Retrograde migration maintains TRM homeostasis between the lung and draining lymph nodes (dLN) following IAV re-infection. (IMAGE)
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Upon IAV infection, lung CD8⁺ tissue-resident memory T (TRM) cells upregulate residency-associated gene signatures but exhibit increased apoptosis. A subset of these cells undergoes CCR5–CCL5 axis-dependent retrograde migration from the lung to the dLN, where they are maintained with reduced apoptotic activity and preserved TRM transcriptional identity. During secondary challenge, dLN TRM cells become reactivated, re-differentiate into TRM, and replenish the local TRM pool. This retrograde migration supports the dynamic maintenance of antiviral TRM populations in the respiratory tract.
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