Regulatory T cells (T_regs) use multiple mechanisms to attenuate inflammation and prevent autoimmunity. T_regs residing in peripheral (i.e., nonlymphoid) tissues have specialized functions; specifically, skin T_regs promote wound healing, suppress dermal fibrosis, facilitate epidermal regeneration, and augment hair follicle cycling. Here, we demonstrated that skin T_regs were transcriptionally attuned to interact with their tissue environment through increased expression of integrin and TGF-β pathway genes that influence epithelial cell biology. We identified a molecular pathway where skin T_regs license keratinocytes to promote innate inflammation after skin barrier breach. Using a single-cell discovery approach, we identified preferential expression of the integrin αvβ8 on skin T_regs. Upon skin injury, T_regs used this integrin to activate latent TGF-β, which acted directly on epithelial cells to promote CXCL5 production and neutrophil recruitment. Induction of this circuit delayed epidermal regeneration but provided protection from Staphylococcus aureus infection across a compromised barrier. Thus, αvβ8-expressing T_regs in the skin, somewhat paradoxical to their canonical immunosuppressive functions, facilitated inflammation acutely after loss of barrier integrity to promote host defense against infection.

调节性 T 细胞 (T _regs ) 使用多种机制来减轻炎症和预防自身免疫。位于外周（即非淋巴）组织中的T _{regs具有特殊功能；}具体来说，皮肤 T _regs促进伤口愈合、抑制真皮纤维化、促进表皮再生和增强毛囊循环。在这里，我们证明了皮肤 T _regs通过增加影响上皮细胞生物学的整合素和 TGF-β 通路基因的表达，在转录上与组织环境相互作用。我们确定了一种分子途径，其中皮肤 T _regs许可角质形成细胞在皮肤屏障破坏后促进先天性炎症。使用单细胞发现方法，我们确定了整合素 αvβ8 在皮肤 T _regs上的优先表达。在皮肤损伤时，T _regs使用这种整合素来激活潜在的 TGF-β，后者直接作用于上皮细胞以促进 CXCL5 的产生和中性粒细胞的募集。该电路的诱导延迟了表皮再生，但提供了保护，防止金黄色葡萄球菌感染穿过受损的屏障。因此，皮肤中表达 αvβ8 的 T _regs与其典型的免疫抑制功能有些矛盾，在屏障完整性丧失以促进宿主对感染的防御后迅速促进炎症。