TY - JOUR
T1 - Human retinoic acid-regulated CD161+ regulatory T cells support wound repair in intestinal mucosa
AU - Povoleri, Giovanni A M
AU - Nova-Lamperti, Estefania
AU - Scottà, Cristiano
AU - Fanelli, Giorgia
AU - Chen, Yun-Ching
AU - Becker, Pablo D
AU - Boardman, Dominic
AU - Costantini, Benedetta
AU - Romano, Marco
AU - Pavlidis, Polychronis
AU - McGregor, Reuben
AU - Pantazi, Eirini
AU - Chauss, Daniel
AU - Sun, Hong-Wei
AU - Shih, Han-Yu
AU - Cousins, David J
AU - Cooper, Nichola
AU - Powell, Nick
AU - Kemper, Claudia
AU - Pirooznia, Mehdi
AU - Laurence, Arian
AU - Kordasti, Shahram
AU - Kazemian, Majid
AU - Lombardi, Giovanna
AU - Afzali, Behdad
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055977347&partnerID=8YFLogxK
U2 - 10.1038/s41590-018-0230-z
DO - 10.1038/s41590-018-0230-z
M3 - Article
C2 - 30397350
SN - 1529-2908
VL - 19
SP - 1403
EP - 1414
JO - Nature Immunology
JF - Nature Immunology
IS - 12
ER -