012 Tissue-specific manipulation of regulatory T cells reveals the skin to be a site of immune tolerance

It is commonly accepted that immune tolerance to self-antigens occurs in the thymus and secondary lymphoid organs. Despite presence of rich microenvironments non-lymphoid organs, such as skin gut, it currently unknown if self-tolerance actively maintained these tissues. We developed a novel technique induce genetic recombination only regulatory T cells (Tregs) reside skin. Cell lineage-tracing revealed Tregs undergo significant attrition replenishment during their natural life cycle. Deletion resulted autoimmune attack hair follicles, by both CD4+ effector CD8+ cells. Suppressive capacity partially relied on high affinity interleukin-2 receptor (CD25) expression Tregs, functioning exclusively cell extrinsic manner. Interestingly, CTLA-4 was completely dispensable for Treg function steady-state In model follicle stem cell-associated autoimmunity, we reveal play critical role immunologically protecting this niche. Collectively, results delineate peripheral tissue relative systemic cellular pool elucidate mechanism active organ.