Epithelial HVEM promotes basement membrane synthesis and intraepithelial T cell survival and migration
Takahashi, D.; Wang, Q.; Seo, G.-Y.; Shui, J.-W.; Mikulski, Z.; Marcovecchio, P.; Takahashi, M.; Surh, C. D.; Cheroutre, H.; Kronenberg, M.
Show abstract
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 TCR{beta}+ cells lacking CD4 and CD8{beta}. Patrolling movement of all CD8+ 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 {beta}1 integrins expressed by the IET; absence of {beta}1 integrins decreased some IET subsets. Therefore, these data define a circuit whereby epithelial cells regulate intestine resident T lymphocyte populations through basement membrane synthesis.
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