Epithelial HVEM promotes basement membrane synthesis and intraepithelial T cell survival and migration
Epithelial HVEM promotes basement membrane synthesis and intraepithelial T cell survival and migration
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DOI：
10.1101/2020.09.30.317628
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发表时间：
2020-10
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影响因子：
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通讯作者：
D. Takahashi;Qingyang Wang;Goo-Young Seo;J. Shui;Z. Mikulski;Paola M. Marcovecchio;Masumi Takahashi;C. Surh;H. Cheroutre;M. Kronenberg
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文献类型：
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作者：
D. Takahashi;Qingyang Wang;Goo-Young Seo;J. Shui;Z. Mikulski;Paola M. Marcovecchio;Masumi Takahashi;C. Surh;H. Cheroutre;M. Kronenberg
上皮内T细胞（IET）提供了持续的监测肠上皮，但很少有人知道如何上皮源性信号调节IET人口。我们发现，上皮细胞表达的疱疹病毒进入介质（HVEM），TNF受体超家族（TNFRSF）的成员，维持小肠IET的生存，特别是缺乏CD 4和CD 8 β的先天样TCRαβ+细胞。在HVEM缺失的情况下，所有CD 8 α+ IET的巡逻运动也受到损害。HREM缺陷的上皮细胞表现出下调的基底膜成分，包括胶原IV的合成。IV型胶原通过与IET表达的β1整联蛋白相互作用支持IET的体外存活; β1整联蛋白的缺失降低了一些IET亚群。因此，这些数据定义了上皮细胞通过基底膜合成调节肠道驻留T淋巴细胞群体的回路。
Intraepithelial T cells (IET) provide continuous surveillance of the intestinal epithelium, but little was known about how epithelial-derived signals regulate the IET population. We show that epithelial expression of the herpes virus entry mediator (HVEM), a member of the TNF receptor superfamily (TNFRSF), maintained the survival of small intestine IET, especially innate-like TCRαβ+ cells lacking CD4 and CD8β. Patrolling movement of all CD8α+ IET also was impaired in the absence of HVEM. HVEM-deficient epithelial cells exhibited downregulation of synthesis of basement membrane components, including collagen IV. Collagen IV supported IET survival in vitro via interactions with β1 integrins expressed by the IET; absence of β1 integrins decreased some IET subsets. Therefore, these data define a circuit whereby epithelial cells regulate intestine resident T lymphocyte populations through basement membrane synthesis.