Adaptive immunity to retroelements promotes barrier integrity [bulk_DC_KC_LC]

The skin is the body’s largest and outermost barrier tissue. Whether environmental exposures reinforce barrier resilience remains poorly understood. Here, we show that xenobiotic-induced retroelement-specific immunity enhances tissue repair; more specifically, mild detergent exposure promotes the reactivation of defined retroelements, and retroelement-specific CD8+ responses, in a Langerhans cell-dependent manner. This discrete population of retroelement-specific CD8 T cells are recruited to the skin, where they develop as tissue-resident cells and are enriched for genes associated with wound repair. Upon injury, retroelement-specific CD8+ T cells significantly accelerate wound repair via IL-17A. Collectively, this work demonstrates that tonic environmental exposures promote the accumulation of tissue-resident retroelement-specific T cells that preemptively set the tissue for maximal resilience to barrier breaches.