Regulatory T cells promote innate inflammation after skin barrier breach via TGF-β activation.
Regulatory T cells promote innate inflammation after skin barrier breach via TGF-β activation.
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DOI：
10.1126/sciimmunol.abg2329
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发表时间：
2021-08-27
影响因子：
24.8
通讯作者：
Rosenblum MD
中科院分区：
文献类型：
--
作者：
Moreau JM;Dhariwala MO;Gouirand V;Boda DP;Boothby IC;Lowe MM;Cohen JN;Macon CE;Leech JM;Kalekar LA;Scharschmidt TC;Rosenblum MD
调节性T细胞（Tcells）利用多种机制来减轻炎症和预防自身免疫。驻留在外周（即非淋巴）组织中的TdR具有专门的功能，特别是皮肤TdR促进伤口愈合，抑制真皮纤维化，促进表皮再生和增加毛囊循环。在这里，我们证明了皮肤TCLs通过增加影响上皮细胞生物学的整合素和TGF-β途径基因的表达而在转录上与其组织环境相互作用。我们确定了一种分子途径，其中皮肤调节性T细胞允许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，我们鉴定了整合素αvβ8在皮肤T细胞上的优先表达。在皮肤损伤后，Tibetan利用这种整合素激活潜伏的TGF-β，其直接作用于上皮细胞以促进CXCL 5产生和中性粒细胞募集。该回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，在皮肤中表达αvβ8的Tcl 3，与其典型的免疫抑制功能有些矛盾，在屏障完整性丧失后急性促进炎症，以促进宿主对感染的防御。表皮损伤后，皮肤中的调节性T细胞从角质形成细胞急性释放促炎信号。
Regulatory T cells (Tregs) utilize multiple mechanisms to attenuate inflammation and prevent autoimmunity. Tregs residing in peripheral (i.e. nonlymphoid) tissues have specialized functions, specifically skin Tregs promote wound healing, suppress dermal fibrosis, facilitate epidermal regeneration and augment hair follicle cycling. Here, we demonstrated that skin Tregs 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 Tregs license keratinocytes to promote innate inflammation following skin barrier breach. Using a single cell discovery approach, we identified preferential expression of the integrin αvβ8 on skin Tregs. Upon skin injury, Tregs utilized 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 Tregs in skin, somewhat paradoxical to their canonical immunosuppressive functions, facilitated inflammation acutely after loss of barrier integrity to promote host defense against infection. Regulatory T cells in skin license pro-inflammatory signaling from keratinocytes acutely following epidermal injury.
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影响因子：
23.9
作者：
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通讯作者：
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