Stage-dependent interaction between circulating and tissue-resident memory CD4⁺ T cells in recurrent allergic airway...

Asthma exacerbation remains a major clinical challenge, yet the immunological mechanisms sustaining recurrent airway inflammation are incompletely understood. In particular, how circulating and tissue-resident memory T-cell populations coordinate systemic recall responses and local persistence during disease relapse remains unclear. To address this, a total of 16 patients with acute asthma exacerbations following a thunderstorm-associated pollen surge and 26 with well-controlled asthma during the same period were enrolled, and the memory CD4⁺ T-cell subsets in the peripheral blood were quantifies. In parallel, an Artemisia (Art)-induced murine model of recurrent allergic airway inflammation was established, in which lymphocyte trafficking was pharmacologically inhibited using FTY720 to dissect the respective contributions of tissue-associated and circulating memory T-cell compartments. Children with acute asthma exacerbations exhibited increased frequencies of circulating CCR4⁺CRTH2⁺ Th2-like memory CD4⁺ T cells, which were associated with enhanced type 2 inflammatory markers and impaired lung function. Repeated allergen exposure induced the persistence of lung tissue-resident memory CD4⁺ T cells together with the re-expansion of circulating memory T cells upon recall challenge. Blockade of lymphocyte egress during the primary phase resulted in only modest attenuation of airway inflammation, whereas sustained blockade during both priming and recall phases effectively suppressed airway inflammation and airway hyper-responsiveness. Collectively, these findings reveal a stage-dependent orchestration of tissue-resident and circulating memory T-cell responses in asthma exacerbation, highlighting the necessity of temporally coordinated therapeutic strategies to achieve sustained disease control.