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

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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Povoleri GAM,Nova-Lamperti E,Scottà C,Fanelli G,Chen YC,Becker PD,Boardman D,Costantini B,Romano M,Pavlidis P,McGregor R,Pantazi E,Chauss D,Sun HW,Shih HY,Cousins DJ,Cooper N,Powell N,Kemper C,Pirooznia M,Laurence

doi

10.1038/s41590-018-0230-z

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

1403-1414

issue

12

eissn

1529-2908

issn

1529-2916

pii

10.1038/s41590-018-0230-z

journal_volume

19

pub_type

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