Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β.
Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β.
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位于屏障上皮内的免疫系统细胞提供了抵抗病原体的第一道防线。朗格汉斯细胞（LCs）和CD8+组织驻留记忆T细胞（TRM细胞）需要活性转化生长因子-β1 （TGF-β）来维持表皮驻留。本研究发现，整合素αvβ6和αvβ8在角质形成细胞（KCs）中以非重叠模式表达，并通过激活潜伏的TGF-β来维持LCs和TRM细胞的表皮驻留。同样，树突状细胞和TRM细胞在小肠上皮内的驻留也需要αv - β6。紫外线照射皮肤可降低KCs上整合素的表达，降低活性TGF-β的可用性，导致LC迁移。我们的数据表明，基质细胞调节TGF-β的激活能够通过细胞间通讯的新机制直接控制免疫系统细胞的上皮驻留。
Cells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8+ tissue-resident memory T cells (TRM cells) require active transforming growth factor-β1 (TGF-β) for epidermal residence. Here we found that integrins αvβ6 and αvβ8 were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and TRM cells by activating latent TGF-β. Similarly, the residence of dendritic cells and TRM cells in the small intestine epithelium also required αvβ6. Treatment of the skin with ultraviolet irradiation decreased integrin expression on KCs and reduced the availability of active TGF-β, which resulted in LC migration. Our data demonstrated that regulated activation of TGF-β by stromal cells was able to directly control epithelial residence of cells of the immune system through a novel mechanism of intercellular communication.
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