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 reg ) cells as a distinct, highly suppressive population of T reg cells that mediate wound healing. These T reg cells were enriched in intestinal lamina propria, particularly in Crohn’s disease. CD161 + T reg cells had an all-trans retinoic acid (ATRA)-regulated gene signature, and CD161 expression on T reg 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 reg cell signature in Crohn’s disease mucosa associated with reduced inflammation. These findings identify CD161 + T reg cells as a population involved in controlling the balance between inflammation and epithelial barrier healing in the gut.
Human retinoic acid–regulated CD161 + regulatory T cells support wound repair in intestinal mucosa / Povoleri, G. A. M.; Nova-Lamperti, E.; Scotta, C.; Fanelli, G.; Chen, Y. -C.; Becker, P. D.; Boardman, D.; Costantini, B.; Romano, M.; Pavlidis, P.; Mcgregor, R.; Pantazi, E.; Chauss, D.; Sun, H. -W.; Shih, H. -Y.; Cousins, D. J.; Cooper, N.; Powell, N.; Kemper, C.; Pirooznia, M.; Laurence, A.; Kordasti, S.; Kazemian, M.; Lombardi, G.; Afzali, B.. - In: NATURE IMMUNOLOGY. - ISSN 1529-2908. - ELETTRONICO. - 19:12(2018), pp. 1403-1414. [10.1038/s41590-018-0230-z]
Human retinoic acid–regulated CD161 + regulatory T cells support wound repair in intestinal mucosa
Fanelli G.;Costantini B.;Kordasti S.Formal Analysis
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2018-01-01
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 reg ) cells as a distinct, highly suppressive population of T reg cells that mediate wound healing. These T reg cells were enriched in intestinal lamina propria, particularly in Crohn’s disease. CD161 + T reg cells had an all-trans retinoic acid (ATRA)-regulated gene signature, and CD161 expression on T reg 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 reg cell signature in Crohn’s disease mucosa associated with reduced inflammation. These findings identify CD161 + T reg cells as a population involved in controlling the balance between inflammation and epithelial barrier healing in the gut.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
