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.

doi:10.1101/2020.09.30.317628

bioRxiv · 10.1101/2020.09.30.317628

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.

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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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Takahashi, D., Wang, Q., Seo, G.-Y., Shui, J.-W., Mikulski, Z., Marcovecchio, P., Takahashi, M., Surh, C. D., Cheroutre, H., Kronenberg, M.. 2020-10-01. Epithelial HVEM promotes basement membrane synthesis and intraepithelial T cell survival and migration. https://doi.org/10.1101/2020.09.30.317628

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