Human retinoic acid-regulated CD161 + regulatory T cells support wound repair in intestinal mucosa

Nat Immunol. 2018 Dec;19(12):1403-1414. doi: 10.1038/s41590-018-0230-z. Epub 2018 Nov 5.

Abstract

Repair of tissue damaged during inflammatory processes is key to the return of local homeostasis and restoration of epithelial integrity. Here we describe CD161+ regulatory T (Treg) cells as a distinct, highly suppressive population of Treg cells that mediate wound healing. These Treg cells were enriched in intestinal lamina propria, particularly in Crohn's disease. CD161+ Treg cells had an all-trans retinoic acid (ATRA)-regulated gene signature, and CD161 expression on Treg cells was induced by ATRA, which directly regulated the CD161 gene. CD161 was co-stimulatory, and ligation with the T cell antigen receptor induced cytokines that accelerated the wound healing of intestinal epithelial cells. We identified a transcription-factor network, including BACH2, RORγt, FOSL2, AP-1 and RUNX1, that controlled expression of the wound-healing program, and found a CD161+ Treg cell signature in Crohn's disease mucosa associated with reduced inflammation. These findings identify CD161+ Treg cells as a population involved in controlling the balance between inflammation and epithelial barrier healing in the gut.

Publication types

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

MeSH terms

  • Crohn Disease / immunology
  • Humans
  • Intestinal Mucosa / immunology*
  • NK Cell Lectin-Like Receptor Subfamily B / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Tretinoin / immunology*
  • Wound Healing / immunology*

Substances

  • KLRB1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily B
  • Tretinoin