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

Nat Immunol. 2016 Apr;17(4):414-21. doi: 10.1038/ni.3396. Epub 2016 Feb 22.

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 (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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Movement
  • Epidermal Cells
  • Epidermis / immunology*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Immunity, Mucosal
  • Integrins / immunology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Intestine, Small / cytology
  • Intestine, Small / immunology
  • Keratinocytes / immunology*
  • Langerhans Cells / cytology
  • Langerhans Cells / immunology*
  • Mice
  • Mice, Knockout
  • Mink
  • Polymerase Chain Reaction
  • Stromal Cells
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta1 / immunology

Substances

  • Antigens, Neoplasm
  • Integrins
  • TGFB1 protein, human
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • integrin alphavbeta6
  • integrin alphavbeta8