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. 2026 Feb 26;18(3):252. doi: 10.21037/jtd-2025-1-2491

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.