• Early RSV infection sustains asthma exacerbation for at least six weeks, with elevated Th2 cytokine secretion in lung tissue.
• CD45–CD4+ tissue-resident memory T cells (TRMs) are positively correlated with RSV-related asthma exacerbation and severe airway inflammation.
• PLZF overexpression increases CD4+ TRM cell numbers, while conditional knockout of Zbtb16 reduces them, modulating allergic inflammation and Th2 responses.
• The study identifies PLZF as a potential therapeutic target for asthma, suggesting combined strategies for patient benefit.