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

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Giovanni A M Povoleri, Estefania Nova-Lamperti, Cristiano Scottà, 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 & 5 more Arian Laurence, Shahram Kordasti, Majid Kazemian, Giovanna Lombardi, Behdad Afzali

Original languageEnglish
Pages (from-to)1403–1414
JournalNature Immunology
Volume19
Issue number12
Early online date5 Nov 2018
DOIs
Accepted/In press7 Sep 2018
E-pub ahead of print5 Nov 2018
Published1 Dec 2018

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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.

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