Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β

Javed Mohammed, Lalit K. Beura, Aleh Bobr, Brian Astry, Brian Chicoine, Sakeen W. Kashem, Nathan E. Welty, Botond Z. Igyártó, Sathi Wijeyesinghe, Emily A. Thompson, Catherine Matte, Laurent Bartholin, Alesia Kaplan, Dean Sheppard, Alina G. Bridges, Warren D. Shlomchik, David Masopust, Daniel H. Kaplan

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85 Scopus citations

Abstract

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 (T RM cells) require active transforming growth factor-β1 (TGF-β) for epidermal residence. Here we found that integrins α v β 6 and α v β 8 were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and T RM cells by activating latent TGF-β. Similarly, the residence of dendritic cells and T RM cells in the small intestine epithelium also required α v β 6. 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.

Original languageEnglish (US)
Pages (from-to)414-421
Number of pages8
JournalNature immunology
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2016

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    Mohammed, J., Beura, L. K., Bobr, A., Astry, B., Chicoine, B., Kashem, S. W., Welty, N. E., Igyártó, B. Z., Wijeyesinghe, S., Thompson, E. A., Matte, C., Bartholin, L., Kaplan, A., Sheppard, D., Bridges, A. G., Shlomchik, W. D., Masopust, D., & Kaplan, D. H. (2016). Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β. Nature immunology, 17(4), 414-421. https://doi.org/10.1038/ni.3396