Journal
NATURE IMMUNOLOGY
Volume 19, Issue 12, Pages 1403-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-018-0230-z
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Funding
- Wellcome Trust [097261/Z/11/Z, WT101159]
- Crohn's and Colitis Foundation of America [3765 - CCFA]
- British Heart Foundation [RG/13/12/30395]
- Purdue University
- National Heart, Lung, and Blood Institute [5K22HL125593-02]
- National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' National Health Service (NHS) Foundation Trust
- King's College London
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Heart, Lung, and Blood Institute of the National Institutes of Health
- Intramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZIAHL006223, K22HL125593, ZICHL006228] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [ZIHAR041173] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [ZIADK075149] Funding Source: NIH RePORTER
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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 Treg 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, ROR gamma t, 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.
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