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

GAM Povoleri, E Nova-Lamperti, C Scottą… - Nature …, 2018 - nature.com
GAM Povoleri, E Nova-Lamperti, C Scottą, G Fanelli, YC Chen, PD Becker, D Boardman
Nature immunology, 2018nature.com
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 …
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.
nature.com