Adaptive immunity to retroelements promotes barrier integrity [bulk_CD8]

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. RNA-seq from CD8+ T cells (CCR6+ and CCR6-) from ear skin of mice treated with HSV1 (CCR6- cells) and BHI-tween (CCR6+ cells)