Inflammatory memory: the core mechanism driving allergic asthma recurrence and chronicity
Review Article

Inflammatory memory: the core mechanism driving allergic asthma recurrence and chronicity

Xu Liu, Ming Zhu, Qianyue Jing, Man Jia, Xin Yao

Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Contributions: (I) Conception and design: X Liu, M Jia, X Yao; (II) Administrative support: X Yao; (III) Provision of study materials or patients: M Zhu, Q Jing; (IV) Collection and assembly of data: M Zhu, Q Jing, X Liu; (V) Data analysis and interpretation: X Liu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Xin Yao, PhD; Man Jia, PhD. Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China. Email: yaoxin@njmu.edu.cn; jiaman@njmu.edu.cn.

Abstract: Advances in biomarker discovery, inhalation therapy, biologics, and bronchial thermoplasty have significantly improved the clinical prognosis and symptom control in patients with asthma. However, recurrence and chronicity of the disease after treatment withdrawal is still a core challenge in clinical management. The emerging concept of inflammatory memory has provided a new perspective for understanding the recurrent remission-relapse cycle in asthma. During asthma onset and development, immune cells and airway structural cells acquire persistent pathogenic memory traits through epigenetic and metabolic reprogramming, thereby amplifying the efficacy of allergen recognition and presentation resulting in local memory niches. These reduce the threshold for airway responses and mediate irreversible airway structural remodeling. In addition, infection, as a key environmental factor, modulates both asthma susceptibility and severity through cross-antigen activation, immune skewing and epigenetic training. Evidence from animal studies suggests that current therapies (especially biological agents) may have the potential to modulate long-resident pathogenic memory immune cells by targeting key cells and inflammatory pathways. However, there are still clinical challenges in the application from animal models to asthma patients. Future interventions should focus on targeting the formation, maintenance, and reactivation of inflammatory memory to attenuate the potential pathogenic memory program in asthma. In this review, we systematically discuss the multi-layered mechanisms of inflammatory memory in asthma pathogenesis, emphasizing the importance of exploring novel strategies for inflammatory memory intervention toward achieving long-term remission.

Keywords: Inflammatory memory; asthma; epigenetic; recurrence; tissue-resident memory T cell (TRM)

Submitted Nov 27, 2025. Accepted for publication Feb 10, 2026. Published online Feb 26, 2026.

doi: 10.21037/jtd-2025-1-2491

Introduction

Allergic asthma is an airway inflammatory disease characterized by recurrent exacerbations and chronic persistence. Current international guidelines recommend a stepwise treatment approach based on inhaled corticosteroids (ICSs), with the long-term goals focused on achieving good symptom control and minimizing acute attacks (1). However, studies indicate that asymptomatic asthma patients in clinical remission still exhibit persistent airway inflammation and structural remodeling, and remain at risk of disease relapse and progressive lung function decline (2,3). Additionally, a clinical cohort study of Chinese patients with moderate-to-severe asthma demonstrated that despite medium-to-high dose ICS therapy, over half (63.8%) of the subjects remain symptomatically uncontrolled (4). A key clinical question therefore remains: why do the airways remain in a hypersensitive state even after inflammation resolves? This indicates that the pathology of asthma involves more than transient inflammatory responses.

When pathogens or allergens invade, innate immune cells rapidly recognize and phagocytose these agents, presenting antigens to T cells and thereby bridging innate and adaptive immunity (5,6). T and B lymphocytes can further differentiate into memory cells, producing antigen-specific antibodies to confer long-term protection (7,8). These long-lived memory T and B cells, residing in lymph nodes and tissues, represent the core of traditional immunological memory and play a central role in the recurrence of chronic inflammatory diseases such as psoriasis and asthma (9-11). Recent research has revealed that immune memory is not confined to adaptive immunity. Even in plants and invertebrates, which lack adaptive immunity, innate immune cells can exhibit memory-like properties. For instance, plants exhibit a memory effect through effector-triggered immunity (ETI), generating mobile immune signals that spread systemically, leading to systemic acquired resistance (SAR) (12-14). In 2011, Mihai Netea’s team first proposed the term “trained immunity”, referring to the phenomenon that innate immune cells undergo epigenetic and metabolic reprogramming after an initial stimulus, leading to a stronger and broader response upon secondary challenge (15). In allergic diseases, early-life exposures, such as to farm environments, microbes, or certain vaccines, including trained immunity-based vaccines (TIbV) and allergen immunotherapy (AIT), may induce trained immunity and reduce allergy susceptibility (16-18); conversely, maladaptive immune memory can contribute to persistent chronic airway inflammation (19). Notably, memory mechanisms are not exclusive to immune cells. After inflammation resolves, structural cells (e.g., skin keratinocytes, airway and intestinal epithelial cells) can retain a “memory” of prior inflammatory events through epigenetic modifications, metabolic reprogramming, and tissue remodeling, actively maintaining a state of dysregulated repair and inflammation (20,21).

The novel concept of “inflammatory memory” posits that both immune cells (e.g., T and B lymphocytes, macrophages) and airway structural cells develop a long-term memory effect following an initial inflammatory insult. This memory lowers the reaction threshold of the airways to stimuli such as allergens or respiratory viruses, enabling a rapid inflammatory outbreak upon re-exposure, bypassing the initial sensitization phase, and thereby driving the recurrence of asthma symptoms. As understanding of the role of inflammatory memory in asthma relapse deepens, the management concept is shifting from suppressing downstream inflammatory responses toward intervening in key pathways of inflammation initiation, amplification, and memory formation. Consequently, the treatment goal is gradually changing from “symptom control” to “clinical remission” (2,22). Notably, the monoclonal antibody tezepelumab, by targeting the key upstream alarmin thymic stromal lymphopoietin (TSLP), disrupts multiple downstream inflammatory cascades and is thus effective across a broad range of asthma phenotypes. In patients with severe, uncontrolled asthma, long-term tezepelumab therapy has been shown to promote complete clinical response and sustained remission (23-25). After 40 weeks of treatment withdrawal, biomarkers including blood eosinophil count (BEC), fractional exhaled nitric oxide (FeNO), and serum total immunoglobulin E (IgE) increased but remained below baseline levels, with 22% of patients maintaining clinical remission (26). These findings suggest that tezepelumab may interfere with the initiation of type 2 inflammation and the formation of downstream immune memory. However, whether tezepelumab can eliminate the established inflammatory memory and achieve long-term recurrence-free status after treatment withdrawal requires verification through longer follow-up studies.

This review highlights the natural history of asthma pathogenesis to elucidate how inflammatory memory originates from early allergen sensing and immune cell activation, and how it ultimately leads to airway dysfunction and irreversible structural remodeling. By integrating this process, we discussed the role of inflammatory memory in the asthma remission-recurrence cycle, and explored therapeutic strategies targeting the inflammatory memory pathway.

Starting point: the “memory amplification” in allergen recognition and presentation

A hallmark of allergic asthma is the abnormally rapid and intense immune response triggered by re-exposure to allergens, reflecting a “memory amplification effect” that arises during the initial phase of allergen recognition and presentation.

This “memory amplification effect” originates from multiple levels. At the epigenetic priming level, chromatin regions (“memory domains”) that open during the initial inflammatory response in immune and structural cells are bound by stress-related transcription factors of the AP-1 family (e.g., the FOS-JUN dimer). These proteins act as pioneer factors that enable the recruitment of other transcription factors and histone modifying enzymes leading to localized post-translational modifications such as H3K4me2, H3K4me3, and H3K27ac that open up the DNA structure and persist long after the initial inflammatory stimulus resolves. Thus, the chromatin accessibility is maintained which enables cells to respond rapidly to subsequent stimuli (Figure 1) (27-29).

Figure 1 Cellular and molecular memory of airway inflammation. Immune cells and structural cells in lung tissue sense and respond to pathogens, allergens, and stimuli. Through epigenetic and metabolic reprogramming, they remain a “memory” phenotype during the remission period after initial stimulus withdrawal. These “primed” state cells can respond more rapidly and strongly to secondary challenges, thereby providing anti-pathogen and pro-repair functions. However, maladaptive immune responses contribute to the persistence of chronic airway inflammation and airway irreversible structural remodeling. ATP, adenosine triphosphate; Ac, acetylation; DCs, dendritic cells; MBC, memory B cell; Me, methylation; M2, M2-polarized macrophages; SMC, smooth muscle cell; TAD, topologically associating domain; TCA, tricarboxylic acid.

At the allergen perception and response level, airway epithelial cells (AECs) that have experienced inflammation exhibit persistent, widespread DNA methylation of asthma-associated genes further allowing AP-1 binding sites to remain accessible. These AECs are considered to be in a “primed” state, which is characterized by heightened sensitivity to allergens or environmental stimuli and enables the accelerated release of alarmins such as interleukin (IL)-25, IL-33, and TSLP (Figure 1) (30,31).

At the level of antigen presentation and bridging adaptive immunity, pathogens or allergens that breach the airway epithelial barrier can induce macrophages to develop a memory phenotype with high MHC II expression which undergo metabolic reprogramming. Dependent on the Akt-mTOR-HIF-1α pathway, their energy metabolism shifts from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, resulting in sustained metabolic activation (Figure 1). This trained immunity program enhances their antigen presentation efficiency and co-stimulatory signaling upon secondary allergen contact, thereby more effectively activating downstream immune cells (32-35). In contrast, although dendritic cells (DCs) are the primary antigen-presenting cells (APCs) initiating adaptive immune responses in the airway, direct evidence demonstrating their ability to establish stable, longterm inflammatory memory in asthma remains insufficient. Research has demonstrated that metabolic reprogramming, specifically the shift from oxidative phosphorylation to aerobic glycolysis, is also an important feature of DCs activation and functional maintenance (36,37). In a protective fungal vaccine mouse model, DCs were confirmed to acquire trained immunity through epigenetic modifications, exhibiting enhanced cytokine secretion [e.g., IL-2, interferon (IFN)-γ, IL-4, transforming growth factor (TNF)-α] upon pathogen re-exposure (38). However, whether DCs contribute to the long-term maintenance of inflammatory memory in allergic asthma remains to be elucidated.

These mechanisms collectively enable asthma patients to initiate a strong type 2 (T2) inflammatory response rapidly, even upon exposure to low-dose allergens, resulting in pathological changes such as mucus hypersecretion and eosinophil infiltration that do not usually occur at these doses. Understanding this “memory amplification” at the initial phase is crucial for elucidating asthma susceptibility and developing early intervention strategies.

Core mechanism: the inflammatory cell infiltration and persistent “memory reservoir”

During the formation and persistence of chronic airway inflammation in asthma, the core question remains: why are inflammatory cells not eliminated leading to sustained inflammation and a tendency for recurrence? Multiple immune cell types reside for long periods in the lung forming an inflammatory memory reservoir (39). Tissue-resident memory T cells (TRM) serve as the core local inflammatory memory reservoir. Animal studies have shown that they can persist in lung tissue for months or throughout life following allergen stimulation, and their dysregulated activation drives the recurrence of allergic airway recall responses (40-43). Parabiosis experiments in mice indicate that lung-resident memory B cells (MBCs) persist for weeks after sensitization and can rapidly enhance local IgE responses upon allergen re-exposure (44). Innate immune cells also help sustain inflammatory memory. Mouse studies show that allergen-experienced group 2 innate lymphoid cells (ILC2s) and alveolar macrophages acquire memory-like properties through epigenetic remodeling, persist in the lung for months, and promote the recurrence and chronicity of airway inflammation (35,45,46).

Collectively, both adaptive and innate immune cells not only possess the ability to survive and self-sustain locally but can also be rapidly reactivated upon re-exposure to low doses of allergens. Through their distinct memory mechanisms, these cells collectively establish a persistent foundation for enhanced local airway inflammation (Figure 2).

Figure 2 Tissue-resident cells contributing to inflammatory memory in asthma recurrence. External stimuli such as pathogens, allergens, and air pollutants can impair the airway epithelial barrier and activate epithelial cells to differentiate into a pathological mucus hypersecretory “memory” phenotype. External stimuli and epithelial-derived alarmins (TSLP, IL-33, and IL-25) “train” APCs (DCs and macrophages) to adopt a memory phenotype with high MHC II expression and metabolic conversion to glycolysis, bridging adaptive immune responses. Simultaneously, alarmins induce the transformation of ILC2s into terminally differentiated memory phenotype (CD127−CD45RO+), which coordinates DC/T cell signals in the airway niche to enhance Th2 responses. The iBALT formed in chronic allergic airway inflammation provides a survival niche for TRM cells and promotes the maintenance of their pathogenic phenotype, thereby amplifying type 2 inflammation and driving pathological airway remodeling by promoting mast cell activation and the expression of profibrotic mediators (e.g., Areg). Lung-resident memory B cells rapidly differentiate into plasma cells under the stimulation of T2 cytokines (IL-4, IL-5, or IL-13), maintaining long-term and efficient IgE memory response. Local interactions between immune cells and structural epithelial/mesenchymal cells shape the immunopathological niches around the airway, establishing a long-term memory effect that results in a lower inflammatory signaling threshold upon secondary exposure to stimuli. Airway epithelial cell-derived SCF promotes mast cell activation, and mast cell-derived Areg feeds back on epithelial cells to reinforce airway remodeling and inflammatory memory. APCs, antigen-presenting cells; Areg, amphiregulin; DCs, dendritic cells; iBALT, inducible bronchus-associated lymphoid tissue; IgE, immunoglobulin E; IL, interleukin; ILC2s, group 2 innate lymphoid cells; MHC, major histocompatibility complex; SCF, stem cell factor; TGF, transforming growth factor; Th2, T helper 2; TRM, tissue-resident memory T cells; TSLP, thymic stromal lymphopoietin; T2, type 2.

Antigen-specific memory of adaptive immune cells

TRM: the key local memory reservoir

After the primary immune response, a subset of activated effector T cells persists following antigen clearance and differentiates into memory T cell subsets with distinct migratory and functional characteristics. Based on homing capacity and spatial distribution, these include central memory T cells (TCM), effector memory T cells (TEM), and TRM cells. Their spatial and temporal compartmentalization endows them with dual roles in chronic inflammation (9,47). As a distinct subset, TRM cells express tissue residency-associated molecules (e.g., CD103 and CD69) to anchor within peripheral non-lymphoid tissues, affecting the efficacy of local immune response (48-50).

TRM cells are considered to play a critical role in the initiation and persistent progression of allergic asthma (51). Lung transplantation studies show that non-asthmatic recipients of lungs from asthmatic donors subsequently develop asthma. This confirms that locally resident immune cells are sufficient to drive disease progression, supporting the concept of asthma as a localized disorder (52). Analysis of lung-resident structural-immune cell interactions reveals that the balanced intercellular communication maintained in health is replaced by a T helper 2 (Th2)-dominant pattern in asthma, driving eosinophilic inflammation and airway remodeling (53). In line with this, the majority of CD4+ T cells in the bronchoalveolar lavage fluid (BALF) of asthma patients exhibit a memory phenotype (CD45RO+), which correlates with symptom severity (54,55).

Functionally, after colonization and functional activation, TRM cells can be rapidly activated upon re-exposure to allergens or nonspecific stimuli to produce T2 cytokines such as IL-5 and IL-13, thereby triggering a pathological immune response and asthma recurrence (56). Animal studies further demonstrate that CD69+CCR7− TRM cells can persist long-term in the lungs independently of circulating memory T cells where they mediate airway hyperresponsiveness (AHR) and inflammation upon re-exposure to allergens (40,43,57,58). Innovative applications of a parabiosis system and the house dust mite (HDM) recall model further revealed functional complementarity between lung-resident and circulating memory Th2 cells in asthma recurrence: circulating memory Th2 cells migrate to the lung parenchyma and induce perivascular inflammation, whereas local lung-resident Th2 cells (Th2 TRM) directly trigger airway pathological responses (42,59). Blocking the migration of circulating cells during the initial sensitization phase significantly reduces pulmonary parenchymal TRM cell formation by ~70% and weakens subsequent memory responses. However, chronic allergen exposure establishes a pool of TRM cells in the lung and this population can drive asthma recurrence without relying on replenishment from circulating cells (57).

At the epigenetic level, the genes encoding T2 cytokines (IL-4, IL-5, and IL-13) in Th2 TRM cells are organized within topologically associating domains (TADs). This spatial folding brings the gene cluster into proximity with distant enhancers, enabling rapid transcriptional recall upon re-stimulation. Furthermore, immune gene-priming long non-coding RNAs (IPLs) enhance H3K4me3 and H3K9ac modifications at the promoters and distal regulatory elements of these cytokine genes. This helps retain chromatin accessibility and facilitates the rapid induction of T2 cytokine recall expression (Figure 1) (60,61).

Local cytokines IL-25, IL-33, and TSLP not only participate in the initial inflammatory response but are also crucial for the formation of the functional effector memory phenotype of Th2 TRM cells (62). TSLP promotes the long-term survival and memory response of memory CD4+ T cells by sustaining Bcl-2 expression and modulating epigenetic modification of IL5/IL13 genes (63,64). TSLP also acts on pulmonary DCs to upregulate surface OX40 ligand (OX40L) expression. This interaction with OX40 on T cells induces the differentiation of naive CD4+ T cells into Th2 cells and enhances T2 cytokine production (65). IL-33 can further amplify the TSLP-driven DC-OX40L signaling axis. Furthermore, the IL-33/ST2 signaling pathway specifically drives the recruitment and maintenance of TRM cells (42,66).

In chronic allergic airway inflammation, the formation of ectopic lymphoid structures, known as inducible bronchus-associated lymphoid tissue (iBALT), provides a survival niche for TRM cells (Figure 2). Within this niche, Thy1+IL-7+ lymphatic endothelial cells (LECs) support TRM cells survival and colonization by secreting CCL19/CCL21, IL-7, and IL-33 (67,68). Concurrently, the intercellular interactions between airway-anchored TRM cells and the respiratory epithelium drive the differentiation of CD4+ TRM cells. AECs present antigens derived from diverse external stimuli, thereby guiding the differentiation of heterogeneous CD4+ TRM subsets (69). In a mouse OVA-induced asthma model, research demonstrates that a population of IL-17+ CD4+ TRM cells persists during disease remission. By co-expressing IL-17 and T2 cytokines, they drive mixed granulocyte infiltration and promote the exacerbation of chronic allergic asthma (70). The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort revealed that co-exposure to allergens and pollutants promotes the retention of IL-17+ TRM cells, leads to earlier allergic sensitization, and significantly increases asthma risk (71). Furthermore, IL-9+ pathogenic Th2 cells are detected in the lower respiratory mucosa during asthma exacerbations. These cells amplify T2 inflammation and promote pathological airway remodeling by promoting mast cell activation and expression of profibrotic mediators (Figure 2) (72). Animal models demonstrate the long-term residency (>6 months) of IL-9+ CD4+ TRM cells. TL1A signaling promotes their differentiation into a multi-cytokine phenotype, and blocking either IL-9 or TL1A signaling during recall allergen challenge significantly attenuates airway inflammation (41,73).

Animal models and human studies suggest that targeting TRM cells represents a potential strategy for promoting long-term remission in asthma. At the molecular level, the transcriptional repressor B-cell CLL/lymphoma 6 (Bcl-6) competitively inhibits STAT5 and GATA3 binding to T2 cytokine gene loci, thereby repressing their transcription and maintaining memory cells in a silent state. Epithelial alarmins antagonize Bcl-6 protein expression in TRM cells, breaking immunological silencing and driving asthma recurrence (64,74). The available evidence, primarily derived from animal models and in vitro studies, suggests that Bcl6 may serve as a potential target for modulating pathogenic memory T cells. Regarding costimulatory signaling, OX40L/OX40 interactions between APCs and activated T cells promote the proliferation and survival of pathogenic T cells (65,75,76). Clinical trials demonstrate that Anti-OX40L agents (Amlitelimab) and anti-OX40 agents (Rocatinlimab) show significant efficacy in patients with moderate-to-severe atopic dermatitis. Notably, some studies observe sustained clinical benefit and persistent downregulation of serum Th2 gene signatures even after treatment discontinuation (77,78). Based on success in atopic dermatitis, OX40/OX40L-targeted strategies have expanded into asthma. In a recent Phase II trial (ClinicalTrials.gov NCT05421598), amlitelimab missed its primary endpoint (annualized exacerbation rate at week 48) but significantly reduced exacerbations and improved lung function and asthma control in specific subgroups with heterogeneous inflammation (e.g., eosinophils ≥300 cells/µL and elevated neutrophils). Notably, improvements in symptoms and inflammatory markers persisted in some patients throughout extended follow-up. Although OX40/OX40L monotherapy has shown limited clinical efficacy in asthma, animal studies suggest that simultaneously targeting multiple costimulatory molecules (e.g., OX40L, CD30L, and ICOSL) more effectively suppresses both circulating and TRM (76,79). This strategy prevents airway inflammation from exacerbating upon repeated allergen challenge, offering a novel approach for co-targeting inflammatory memory.

CD8+ T cells: dual roles

CD8+ T cells exhibit functional plasticity in the allergic environment. Conventionally, they are thought to inhibit T2 responses and maintain immune tolerance by secreting IFN-γ and cytotoxic molecules (80,81). However, emerging evidence indicates that long-term allergen exposure impairs the function of CD8+ TEM cells, manifested as an expansion of the S100A4+ subset, diminished IFN-γ secretion, and a loss of protective immunity (82). In severe asthma, especially in steroid-resistant patients, terminally differentiated CD8+ TEM cells are positively correlated with the course of asthma, and drive neutrophil inflammation through IL-15-dependent abnormal proliferation and IFN-γ secretion (83).

Unexpectedly, accumulating evidence from both asthma patients and animal models indicates that CD8+ memory T cells can also exacerbate T2 inflammation. Specific CD8+ TEM subsets (such as IL-6Rα+ or BLT1+IL-13+ cells) can rapidly produce T2 cytokines following viral or bacterial challenge, exacerbating eosinophilic inflammation (84,85). Clinical studies demonstrate that the levels of BLT1+IL-13+ CD8+ T cells in BALF are positively correlated with airway remodeling and impaired lung function. Notably, this cell subset may be associated with corticosteroid-resistant inflammatory phenotypes (86,87). Treatments targeting the leukotriene synthesis pathway, such as 5-lipoxygenase (5-LO) inhibitor zileuton, have been shown to improve lung function and reduce the incidence of symptoms and acute exacerbations (88). Direct clinical evidence is still lacking to confirm that leukotriene pathway blockade specifically modulates CD8+ T cell function. Mechanistic studies in mouse models of allergic AHR indicate that LTB4-BLT1 signaling is essential for recruiting leukotriene-dependent CD8+ T cells and driving their pathogenic function. Blocking this pathway significantly inhibits CD8+ T cell-mediated AHR (89). These findings suggest that evaluating the impact of leukotriene pathway inhibition on CD8+ T-cell effector functions may have significant value in future clinical research.

Lung-resident MBCs: drivers of rapid IgE memory responses

Allergen-specific MBCs, rather than short-lived plasma cells, serve as the primary reservoirs of IgE memory and mediate the long-term maintenance of asthma susceptibility. Upon re-exposure to allergens, MBCs rapidly differentiate into plasma cells, releasing large amounts of allergen-specific IgE while forming positive feedback loops with Th2 cells, thereby amplifying allergic inflammation (Figure 2) (8,10,90).

Different B cell subsets participate in the pathological process of asthma through distinct mechanisms. A population of resident memory IgG1+ B cells has been identified in the lung, which undergoes class-switch recombination dependent on T2 cytokines and drives local IgE responses in the airways (44). In allergic individuals (including those with asthma, food allergy, and atopic dermatitis), a subset of IgG+ T2 polarized memory B cells (MBC2) with high expression of IL-4Rα and CD23 has been identified in both peripheral circulation and local mucosal tissues. These MBC2s are temporally linked to IgE memory responses, rapidly differentiate into pathogenic IgE-producing plasma cells, and play a key role in maintaining long-term IgE memory and the recurrence of allergic inflammation (91-94). Studies have confirmed that IgE+ B cells can also form directly in the germinal center without the intermediate stage of IgG+, explaining the rapid establishment of IgE memory (95). In addition, circulating IgA+ MBCs are elevated in asthma patients with small airway dysfunction and are associated with airway resistance and acute exacerbation, independent of oral corticosteroid use, indicating their potential as novel biomarkers and therapeutic targets (96).

Existing anti-IgE therapies, such as Omalizumab, only neutralize free IgE and fail to eliminate MBCs, which is one of the reasons for easy recurrence after treatment withdrawal (97,98). Based on this limitation, researchers have further explored targeting membrane-bound IgE-expressing MBCs with the aim of fundamentally reducing the pool of IgE-secreting plasma cells (99). Clinical studies show that quilizumab, an anti-IgE-M1 prime membrane-specific monoclonal antibody, reduces serum IgE by depleting MBCs, with partial persistence after treatment cessation, but does not confer significant clinical benefit in adults with inadequately controlled allergic asthma (100,101). Therefore, depleting IgE+ MBCs alone seems insufficient to reverse established airway inflammatory networks and remodeling.

A recent study provided new insights into immune memory plasticity. In a mouse allergic recall model, Bruton et al. showed that blockade of IL-4/IL-13 signaling during the recall phase reprograms established IgE-fated MBCs toward an IFN-γ-dependent, non-pathogenic antibody response, generating durable non-allergic immune memory. This finding offers a potential mechanistic explanation for the sustained clinical benefit observed in some asthma patients after discontinuation of anti-IL-4Rα antibody (dupilumab) therapy (102). Clinical evidence remains insufficient to confirm that these strategies can selectively and durably reshape pathogenic MBCs to yield clinical benefits. Thus, precision targeting of MBCs represents a critical priority for future research.

Non-specific memory of innate immune cells: trained immunity

ILC2s: antigen-nonspecific memory

ILC2s possess antigen-nonspecific memory capabilities and can reside locally long-term within barrier tissues (103). Martinez-Gonzalez et al. first identified a population of allergen-experienced ILC2s, whose transcriptional profile closely resembles that of memory CD8+ T cells. These ILC2s persist long after inflammation resolves and rapidly produce IL-5 and IL-13 upon restimulation, initiating allergic recall responses (45). Furthermore, Steer et al. proposed the concept of trained ILC2s during the neonatal period, also termed neonatal ILC2s, demonstrating that the peak in endogenous lung IL-33 in early-life induces sustained ILC2 activation that persists into adulthood. Unlike allergen-induced memory ILC2s in adults, neonatal ILC2s show only transient IL-25R upregulation, with the alteration being a persistently enhanced sensitivity to IL-33 (104,105).

Local cytokines IL-25, IL-33, and TSLP form a “tissue checkpoint” that induces resting ILC2s (CD45RA+) to differentiate into a memory CD127−CD45RO+ cells, thereby maintaining local immune memory (Figure 2) (62,106). Memory ILC2s can survive in lung tissue for over six months while remaining in an activated state. ILC2 depletion or IL-33 blockade significantly alleviates airway inflammation (46). Memory ILC2 cells still maintain a high level of IL-5/IL-13 mRNA and chromatin opening during inflammatory remission. This depends on TCF/β-catenin and adhesion pathways and helps maintain tissue residency, and enhances T2 responses due to high expression of IL-25R which coordinates DC/T cell signals in the airway niche (107,108).

At the molecular level, memory ILC2 shows a unique epigenetic landscape: memory-related genes of the AP-1 family (Preparedness Program) and Bach2 (Repression Program) balance each other to maintain chromatin accessibility (109). ILC2 cells express a relatively high level of NFκB1 in both allergen sensitization and recall stimulation stages. During the sensitization phase, NFκB1 suppresses excessive memory formation by negatively regulating AP-1 and Bach2. However, it cooperates with RUNX1 to directly activate IL-5/IL-13 transcription during recall challenge, thereby driving disease recurrence (110).

Clinical studies have found that memory CD45RO+ inflammatory ILC2s in the inflammatory mucosa and circulation of patients with chronic sinusitis or asthma showed glucocorticoid resistance, a feature associated with severe asthma. Dupilumab can inhibit the activation of ILC2 and the establishment of memory, offering hope for patients with steroid-insensitive severe asthma (111,112).

Macrophages: TNF-dependent immune memory

Macrophages develop immune memory through epigenetic and metabolic reprogramming. Repeated LPS stimulation can induce gene-specific epigenetic regulation: pro-inflammatory genes become silenced while antimicrobial genes remain accessible, achieving a balance between inflammation control and host defense (113). Allergens trigger long-term macrophage reprogramming through autocrine TNF signaling, characterized by increased amino acids and TCA cycle intermediates, resulting in sustained overproduction of pro-inflammatory mediators including CCL17 and leukotrienes that maintain airway hypersensitivity (Figure 2). This TNF-dependent memory effect can be reversed by anti-TNF therapy (33). In patients with NSAID-exacerbated respiratory disease (N-ERD), macrophages display a persistent pro-inflammatory state with an abnormal metabolic profile characterized by elevated levels of pro-inflammatory lipid mediators, including acylcarnitines and arachidonic acid (114). In addition to its own phenotypic remodeling, macrophage memory is also reflected in an enhanced response to secondary stimuli. HDM-trained macrophages exhibit increased production of macrophage migration inhibitory factor (MIF). Upon subsequent LPS challenge, MIF inhibits p53-mediated apoptosis and promotes M1 polarization, thereby amplifying the release of TNFα and IL-6 and providing a mechanism of infection-associated asthma exacerbation (115).

In addition, cell-cell interactions can drive the establishment of long-term immune memory in lung-resident macrophages. Parasite-induced alternatively activated (N2) phenotype neutrophils drive long-term M2-polarized macrophagesmacrophage residency. Similarly, virus-specific CD8+ T cells train alveolar macrophages via IFN-γ, enhancing neutrophil recruitment (35).

Neutrophils: IL-17-driven memory phenotype

As a rapid responder of innate immunity, terminally differentiated neutrophils are short-lived, but recent evidence from chronic asthma models indicates that lung-resident neutrophils can retain some memory-like properties.

Single-cell RNA sequencing (scRNA-seq) on lung tissues obtained from mice with ovalbumin (OVA)-induced chronic allergic asthma (Th2/Th17 mixed response phenotype) has identified a distinct neutrophil subset exhibiting features of innate immune memory. The Th2/Th17 cytokine microenvironment reprograms lung neutrophils into a memory-like state, resulting in a pro-inflammatory G-CSFR+FcγRIIb+ subset characterized by significant upregulation of innate immune memory molecules. These include Toll-like receptor signaling, antigen presentation genes (H2-K1 and B2m), IL-4 receptor and the key transcription factor C/EBPβ for inflammatory cytokines IL-1β and IL-6. These inflammatory memory neutrophils provide a new perspective for understanding disease severity and glucocorticoid resistance in neutrophilic asthma (116). IL-17 plays a central role in neutrophil recruitment, and animal experiments showed that anti-IL-17 therapy can significantly reduce airway neutrophils (117,118).

Outcome: inflammatory memory-driven AHR and remodeling as “structural memory”

In the pathological process of asthma, why does AHR and structural remodeling persist even during the inflammatory remission phase? Recent studies suggest that the persistence of inflammatory memory not only maintains immune cells in a primed state but also promotes airway remodeling as structural memory including the physical restructuring of the airways, memory-like properties of epithelial cells, and the formation of cellular interaction-based niches (Figure 2) (21,39,119). Together, the pathologically activated state of epithelial cells and the irreversible spatial remodeling of the airways constitute a fundamental basis for the chronicity of asthma.

Physical memory of irreversible airway remodeling

Airway remodeling caused by repeated stimulation of chronic inflammation is the core pathological basis of persistent symptoms and irreversible lung function decline in refractory asthma (120). In addition to phenotypes such as ciliary dysfunction, goblet cell metaplasia, and ECM deposition fibrosis, remodeling constitutes a physical consequence of airway inflammatory memory (121,122).

The cytokine IL-33 selectively activates memory Th2 cells, induces their secretion of amphiregulin (Areg), which induces remodeling through EGFR signaling: high expression of eosinophil-derived osteopontin (OPN), abnormal proliferation of epithelial cells and fibroblasts, and mucus hypersecretion (67,123). Recent spatial transcriptomic studies reveal that even if active anti-inflammatory treatment with inhaled glucocorticoids or with biological agents reduces local cytokine levels, spatial restructuring persists in the airway mucosa. This restructuring features reduced physical distances between basal and endothelial cells, goblet cells and serous cells, resulting in tighter cellular clustering with localized retention of fibroblasts and mast cells, which constitutes the physical basis of inflammatory memory in the respiratory tract (39).

Targeting this spatial remodeling has become a potential therapeutic strategy. Imatinib, a tyrosine kinase inhibitor, can not only significantly prevent AHR and eosinophilic airway inflammation in a mouse model of chronic asthma, but also inhibit airway smooth muscle thickening and collagen deposition (124). In a randomized controlled clinical study of patients with severe refractory asthma, imatinib treatment can reduce AHR. Airway biopsy single-cell spatial transcriptomics further found that Imatinib can increase cell spacing and partially reverse pathological spatial remodeling while inhibiting airway mast cell activity, suggesting that some patients may benefit from intervention in structural inflammatory memory (39,125).

These findings suggest that airway remodeling is not only a consequence, but also a spatial manifestation of inflammatory memory. In barrier tissues such as the respiratory tract, gut, and skin, structural cells store immune experience through epigenetic reprogramming, cell state transition and spatial positional changes, collectively forming the tissue basis for the recurrence of chronic inflammation (121,126).

Airway epithelial memory: epigenetic persistence and pathological remodeling

The concept of inflammatory memory was first demonstrated in skin epithelial stem cells (EpSCs), where the inflammasome core sensor AIM2 mediates enhanced chromatin accessibility of hyperproliferation-associated genes. This effect is retained long after clinical symptoms subside, enabling a rapid secondary response independent of immune cell infiltration (20). Asthmatic epithelial cells also exhibit stable epigenetic memory. After several passages in vitro, induced pluripotent stem cells derived from nasal epithelial cells (NEC-iPSCs) of asthmatic children maintain DNA methylation imprints on pro-remodeling genes such as RPTN and CAT, which are linked to asthma pathogenesis (21). In vitro studies confirm that the basal stem cell differentiation is blocked in a T2 inflammatory environment. These cells maintain high expression of Wnt/CTNNB1 target genes and inflammation-related genes, and their clonal expansion serves as an allergic memory reservoir (31).

The T2 inflammatory cytokine IL-13 induces DNA methylation of asthma-associated genes in AECs, which are clustered into two functionally distinct memory modules: Module 1 is enriched for ERK1/2 signaling and fibrotic pathways, correlating with airway remodeling and disease severity; whereas Module 2 is enriched for IFN-γ and NF-κB inflammatory pathways, driving eosinophil infiltration (30). Chronic IL-13 stimulation induces a pathological mucus secretory program in multiple human AEC subsets. It drives mucus-producing, defense-related SCGB1A1+ cells toward a metaplastic state with excessive mucus production, and concurrently downregulates ciliary motility genes in ciliated cells, leading to endoplasmic reticulum (ER) stress and cell death. Transcriptomic analysis of nasal epithelium from the Genes-Environments & Admixture in Latino Asthmatics (GALA II) childhood asthma cohort has validated this persistent pathological remodeling of epithelial cells (119). Single-cell spatial landscapes of the human airway wall reveal that MUC5B expression in goblet cells is ~340% greater in samples from asthma patients than from healthy samples, and that anti-inflammatory treatment with ICSs or biologics failed to reverse it effectively. Excessive mucin secretion and local mucus plug formation are the core features of asthma pathology, and are present in ~70% of patients with severe asthma (39).

The anti-IL-4Rα monoclonal antibody dupilumab has been shown in human AECs (from chronic type 2 inflammatory disease patients) to down-regulate inflammatory memory genes (e.g., ATF3 and KLF5), inhibit Wnt pathway activity, and shift cellular state from pathological secretion toward healthy direction. Although these findings were obtained in nasal/upper airway epithelium, they may share mechanisms with lower airway asthma epithelial memory. These changes indicate that targeting cytokine signaling can partially reprogram epithelial cell status and reverse inflammatory memory (31).

“Memory niche”: local crosstalk between structural and immune cells

The local inflammatory memory of the respiratory tract depends on a specialized microenvironment, the Memory Niche, which is constructed and maintained by the synergistic interaction of epithelial cells and immune cells (126). The latest research used the Xenium platform and GeoMx spatial transcriptome technology to draw the first single-cell spatial atlas of the human airway wall, providing detailed information on the function, spatial location and intercellular communication of airway wall cell subtypes. This revealed the critical role of airway wall microecology in the remission and recurrence of asthma airway local inflammation. Discrete pro-inflammatory cellular ecosystems within spatial niches are located in the airway subepithelial and mucous gland regions of asthmatic patients. As discussed in section “Antigen-specific memory of adaptive immune cells”, epithelial-derived alarmins regulate immune cell recruitment and persistence within these niches. In the niche, basal cells, goblet cells, and endothelial cells synergistically highly express alarmins and chemokines (e.g., CCL5, CXCL8), regulating the migration and survival of immune cells (39). It is essential to clarify the interaction mechanisms between structural cells and local immune populations to fully understand the persistence of inflammatory memory and determine how this is modified by biologic therapy.

In the neutrophil asthma model induced by chronic allergen exposure, Muc5ac-hypersecreting epithelial cells organize immunopathologic niches, which serve as a bridge connecting TRM cells and neutrophils. On one hand, these epithelial cells present antigens and induce the differentiation of tissue-resident RORγt−/low T helper 17 (Th17) TRM cells; on the other hand, they secrete chemokines CXCL5 and CXCL6, promoting neutrophil infiltration around the airways. The cellular interactions shape the immunopathological microenvironment around the airway, which helps explain the refractoriness of severe asthma in adults (69). Furthermore, mast cell expansion occurs across a spectrum of T2 inflammatory diseases, and their interaction with epithelial cells is also crucial. During allergic airway inflammation, epithelial cell-derived stem cell factor (SCF) promotes the migration and expansion of local CD38highCD117high mast cells from the submucosa into the epithelial layer (127,128). In the subepithelial niche, mast cells persistently express Areg, which activates the EGFR signaling pathway to promote epithelial repair and fibrosis. The sustained high levels of Areg before and after treatment may help maintain a memory state of the pro-inflammatory microenvironment (Figure 2) (39). Local cytokine IL-4 induces mast cells to differentiate into an inflammatory phenotype with high expression of IL-17RB (IL-25 receptor), while mast cells themselves can also produce factors such as IL-13 and CCL2, forming a positive feedback loop that strengthens the local T2 inflammatory environment in the airway (127).

Treatment with the anti-IL-4Rα antibody dupilumab disrupts epithelial-mast cell communication, reduces the inflammatory phenotype of mast cells, and attenuates airway local inflammatory memory effects (127). Recently, researchers have pioneered the spatial drug-target analysis combined with the Drug2Cell tool to predict the microenvironment-specific efficacy of drugs such as tisotumab vedotin (anti-coagulation factor 3) and caplacizumab (anti-von Willebrand factor antibody). The combination of spatial transcriptomics and drug target information offers a new strategy for precisely targeted therapy and personalized treatment (39).

Trigger and modulation: how infection “rewrites” inflammatory memory

The inflammatory memory established by infection plays a complex and contradictory role in asthma. It can either suppress and prevent the onset of asthma or promote disease exacerbation and chronicity. The specific effect depends on the complex interaction between multiple factors, including pathogen type, timing of infection, host genetic background, and the local immune microenvironment (Figure 3).

Figure 3 Dual roles of infection-induced immune memory in asthma. Infection-induced inflammatory memory exerts bidirectional effects on asthma depending on pathogen type, timing of exposure, and the local immune microenvironment. Left panel: early microbial exposures can induce cross-reactive, Th1-skewed immune memory that suppresses type 2 inflammation upon subsequent allergen encounter, reducing asthma susceptibility. Right panel: in contrast, respiratory viral infections, air pollutants, or allergen exposure during susceptible periods can establish pathogenic immune memory characterized by Th2 or Th17 polarization and trained macrophage responses. Upon re-exposure, these memory programs amplify inflammatory cytokine production, promote eosinophil and neutrophil infiltration, and drive airway hyperresponsiveness and remodeling. Conversely, the allergic inflammatory microenvironment in asthma can compromise antiviral immune memory and increase the risk of infection-triggered exacerbations. AHR, airway hyperresponsiveness; APC, antigen-presenting cell; EVA, enterovirus A; IFN, interferon; IL, interleukin; RVC, rhinovirus C; Th1, T helper 1; Th2, T helper 2; Th17, T helper 17; TRM, tissue-resident memory T cells.

From the infection-to-asthma perspective, infection-induced memory T cells can respond to different antigens due to the polyclonality and cross-reactivity of their T cell receptor (TCR), thereby potentially modulating asthma susceptibility in both directions. Animal studies demonstrate that microbial infections (e.g., viral or bacterial) can induce dual-receptor (dualR) memory T cells, potentially providing a mechanistic explanation for the dual effects of pathogen exposure on asthma development (129,130).

Early environmental exposures (e.g., bacteria, fungi, and food proteins) induce cross-reactive adaptive immune memory that imprints a non-Th2-dominant response pattern upon subsequent allergen encounter. This prevents IgE-mediated type 2 polarization, thereby reducing the propensity for allergic sensitization (131). Mechanistically, animal studies demonstrate that virus-induced, allergen-cross-reactive memory Th1 cells can be activated to secrete cytokines such as IFN-γ and IL-2. These mediators suppress eosinophil infiltration and mucus hyperplasia, thereby providing an immunological basis for the hygiene hypothesis (132,133).

Regarding the establishment of pathogenic memory, early respiratory viral infections or environmental pollutant exposure lead to the accumulation of Th2 memory cells in mouse lungs. These cells significantly exacerbate AHR and inflammation during subsequent sensitization and challenge, suggesting that infections may enhance secondary allergen recall responses by reshaping memory T-cell reactivity (71,134). In humans, rhinovirus C (RVC) can induce memory T cells with impaired IFN-γ responsiveness, elevated CCL24 (eotaxin-2) expression, and activation of the IL-17A pathway. These features are related to neutrophilic inflammation and asthma chronicity (135). In addition, early life viral infections (such as RSV) can train lung/bone marrow macrophages to form long-lasting immunopathological memories, manifested by the CD69+TLR4+ phenotype and enhanced glycolytic activity, driving Th1/Th17-biased inflammation and neutrophil infiltration (34,136). Notably, certain pathogens like Staphylococcus aureus can also induce mucosal MBCs to rapidly produce IgE, driving the recurrence of atopic diseases (137,138).

The airway allergic microenvironment can also interfere with antiviral immune memory. In healthy individuals, virus-specific CD8+ TRM cells effectively control reinfection and promote viral clearance (139). However, in the allergic pulmonary microenvironment of asthmatic patients, the formation and function of virus-specific CD8+ TRM cells are inhibited, which weakens their protective immune memory against respiratory viruses, increasing susceptibility to virus-induced acute exacerbations in asthmatic individuals. This phenomenon was confirmed in the U-BIOPRED cohort: patients with enriched epithelial IFN-γ-induced gene were also enriched in TRM-associated genes, with more epithelial CD8+ TRM cells, and significantly fewer exacerbations (140).

In summary, there is a bidirectional and dynamic immunological interplay between infection and asthma. In-depth exploration of the microbial-immune interaction mechanism not only helps to understand the heterogeneity of asthma, but also provides important insights for the development of targeted prevention and treatment strategies and for the identification of high-risk populations.

Discussion

Inflammatory memory provides a key pathophysiological framework for asthma development and relapse. This concept holds that following initial inflammatory exposure, immune and structural cells in the airways undergo lasting adaptive changes, priming the local tissue to mount amplified responses upon re-exposure. Rather than a single causal mechanism, this process facilitates asthma recurrence and persistence by lowering the threshold for inflammatory activation and accelerating effector responses, driven by multiple contributing factors. It begins with memory amplification during allergen sensing, centers on the formation of a long-term resident memory reservoir by immune cells, and ultimately drives the development of “structural memory” in the airway epithelium and tissue. Even during asymptomatic periods, low-level self-sustaining inflammatory circuits and airway remodeling microenvironments can maintain a persistent inflammatory baseline and AHR.

The asthmatic disease process initiates with a memory amplification effect during allergen recognition and presentation whereby AECs and APCs undergo epigenetic and metabolic reprogramming, rapidly triggering downstream T2 inflammatory responses (121). During inflammatory cell infiltration and persistence, antigen-specific TRM cells and MBCs act as core carriers of inflammatory memory. They form a local memory reservoir along with other immune cells such as macrophages and ILC2s that maintain a pro-inflammatory phenotype via trained immunity. These cellular subsets exhibit enhanced survival and reactivation capacity, enabling rapid inflammatory reactions upon re-exposure to stimuli. AECs serve not only as a physical barrier but also as key participants in immune regulation (121). Through spatial and epigenetic remodeling and crosstalk with immune cells, they form a local memory niche that actively perpetuates abnormal repair and sustained inflammation (126). This provides a new perspective on the mechanisms underlying chronic asthmatic inflammation. In summary, the complex bidirectional relationship between infection and asthma is influenced by multiple environmental and genetic factors, involving epigenetic reprogramming in immune and structural cells, antigen cross-reactivity, and local microenvironment alterations (71). The dual role of infection-induced immune memory, which can be either protective or pathogenic, enhances our understanding of asthma heterogeneity.

It should be noted that inflammatory memory is not limited to allergic asthma. In non-allergic asthma, bacterial endotoxins, viral infections, and air pollution can also contribute to persistent AHR and chronic inflammation through epigenetic remodeling of TRM (e.g., Th1/Th17), trained innate immune cells, and structural cells. Therefore, both allergic and non-allergic asthma subtypes share the core framework of “immune memory—tissue residency—structural remodeling” in pathology, and the differences may be reflected in the initial stimulation of memory formation and the dominant immune pathway.

Although our review provides a comprehensive overview of the role of inflammatory memory in the recurrence and chronicity of asthma, there are still some limitations. First, the memory function of some immune cells (such as neutrophils) in asthma is still in the early stage of research, and the evidence is mostly derived from animal models. The direct evidences at the human level still need more research to confirm. Second, current gene editing technologies and immune-based therapies, such as CAR-T and CAR-NK, show promise in targeting pathogenic memory cells in asthma (141,142). CAR-T therapy has shown significant effects in allergic asthma mouse models, with a single injection leading to sustained suppression of lung inflammation for up to a year (142). However, these approaches are still in the preclinical stage and face challenges, including off-target effects, immune escape, limited cell persistence, and the complexity of memory cell subsets. The heterogeneity of asthma further complicates clinical application. There are still technical bottlenecks in how the therapeutic strategies (such as targeted memory cells, epigenetic editing) specifically eliminate pathogenic memory cells without affecting protective immune memory.

Conclusions and future perspectives: targeting “inflammatory memory” in asthma treatment

Current asthma treatments can effectively suppress downstream inflammatory effects and control symptoms, yet fail to eradicate the underlying inflammatory memory or reverse tissue remodeling, resulting in a high risk of disease recurrence after drug withdrawal. In response to this limitation, future treatment approaches need to target the formation of inflammatory memory: reprogramming cell status through epigenetic editing or metabolic intervention; accurately depleting pathogenic memory cells or disrupting their survival and retention signals; and identifying key cell interaction targets to disrupt the memory niches. Such strategies hold promise for shifting the therapeutic goal from “inhibiting inflammation” to “eradicating inflammatory memory”.

As discussed in this review, based on current interventional and clinical evidence, several memory-associated pathways have emerged as actionable therapeutic targets in asthma, including epithelial alarmin signaling (TSLP), costimulatory pathways supporting TRMs (OX40/OX40L), IL-4/IL-13-driven IgE memory B cell programs, and structural memory nodes involving mast cell-KIT signaling (Table 1). Together, these advances support a shift in asthma management from suppressing episodic inflammation toward targeting inflammatory memory itself, with the long-term goal of achieving durable disease remission rather than temporary symptom control.

Table 1

Evidence supporting inflammatory memory-targeted interventions in asthma recurrence and chronicity

Memory cell type or niche Inflammatory memory mechanism Potential therapeutic targets Evidence source Key interventional/clinical observations Relevance to recurrence/chronicity
Tissue-resident memory T cells Sustained costimulatory signaling and local persistence OX40/OX40L blockade (amlitelimab, rocatinlimab) Human and mouse models Modest overall efficacy with enhanced benefit in patient subgroups and persistent suppression of inflammatory gene signatures after treatment withdrawal TRM mediated memory in relapse
IgE-fated memory B cells Long-lived IgE programming and recall responses Anti-M1 prime antibody (quilizumab) Human clinical trials Reduction in circulating IgE producing memory B cells without consistent clinical improvement Limited efficacy of isolated memory B cell depletion
Epithelial memory niche Alarmin driven imprinting of immune memory Anti-TSLP antibody (tezepelumab) Human clinical trials Sustained reduction in exacerbation rates with prolonged benefit in a subset after treatment discontinuation Targeting upstream memory formation to reduce relapse risk
Structural memory niche KIT dependent mast cell persistence and tissue remodeling KIT inhibition (imatinib) Mouse models and human clinical study Reduced airway hyperresponsiveness and partial reversal of airway remodeling Airway spatial remodeling

IgE, immunoglobulin E; KIT, stem cell factor receptor; TRM, tissue-resident memory T cells; TSLP, thymic stromal lymphopoietin.

Acknowledgments

None.

Footnote

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2491/prf

Funding: This work was supported by the National Natural Science Foundation of China (Nos. 82370035, 82170040 and 82200035); the Natural Science Foundation of Jiangsu Province (No. BK20210957); and the China Postdoctoral Science Foundation (No. 2025M772061).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2491/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: Liu X, Zhu M, Jing Q, Jia M, Yao X. Inflammatory memory: the core mechanism driving allergic asthma recurrence and chronicity. J Thorac Dis 2026;18(3):252. doi: 10.21037/jtd-2025-1-2491

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