Human Retinoic Acid-regulated CD161 Regulatory T Cells Support Wound Repair in Intestinal Mucosa

Overview

Journal Nat Immunol

Date 2018 Nov 7

PMID 30397350

Citations 47

Authors

Giovanni A M Povoleri

Estefania Nova-Lamperti

Cristiano Scotta

Giorgia Fanelli

Yun-Ching Chen

Pablo D Becker

Dominic Boardman

Benedetta Costantini

Marco Romano

Polychronis Pavlidis

Reuben McGregor

Eirini Pantazi

Daniel Chauss

Hong-Wei Sun

Han-Yu Shih

David J Cousins

Nichola Cooper

Nick Powell

Claudia Kemper

Mehdi Pirooznia

Arian Laurence

Shahram Kordasti

Majid Kazemian

Giovanna Lombardi

Behdad Afzali

Affiliations

Soon will be listed here.

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 (T) cells as a distinct, highly suppressive population of T cells that mediate wound healing. These T cells were enriched in intestinal lamina propria, particularly in Crohn's disease. CD161 T cells had an all-trans retinoic acid (ATRA)-regulated gene signature, and CD161 expression on T 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 T cell signature in Crohn's disease mucosa associated with reduced inflammation. These findings identify CD161 T cells as a population involved in controlling the balance between inflammation and epithelial barrier healing in the gut.

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