Mohammed Javed, Beura Lalit K, Bobr Aleh, Astry Brian, Chicoine Brian, Kashem Sakeen W, Welty Nathan E, Igyártó Botond Z, Wijeyesinghe Sathi, Thompson Emily A, Matte Catherine, Bartholin Laurent, Kaplan Alesia, Sheppard Dean, Bridges Alina G, Shlomchik Warren D, Masopust David, Kaplan Daniel H
Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
Nat Immunol. 2016 Apr;17(4):414-21. doi: 10.1038/ni.3396. Epub 2016 Feb 22.
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.
驻留在屏障上皮组织中的免疫系统细胞为抵御病原体提供了第一道防线。朗格汉斯细胞（LCs）和CD8⁺组织驻留记忆T细胞（TRM细胞）在表皮驻留需要活性转化生长因子-β1（TGF-β）。我们发现整合素αvβ6和αvβ8在角质形成细胞（KCs）中以不重叠的模式表达，并通过激活潜伏的TGF-β来维持LCs和TRM细胞在表皮的驻留。同样，树突状细胞和TRM细胞在小肠上皮中的驻留也需要αvβ6。用紫外线照射皮肤会降低KCs上整合素的表达，并减少活性TGF-β的可利用性，从而导致LC迁移。我们的数据表明，基质细胞对TGF-β的调控激活能够通过一种新的细胞间通讯机制直接控制免疫系统细胞在上皮组织中的驻留。
