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Nat Immunol. 2018 Dec;19(12):1403-1414. doi: 10.1038/s41590-018-0230-z. Epub 2018 Nov 5.

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

Author information

1
MRC, Centre for Transplantation, King's College London, London, UK.
2
National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
3
Bioinformatics and Computational Biology Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
4
Comprehensive Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
5
Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
6
Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
7
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
8
Department of Infection, Immunity and Inflammation, NIHR Leicester Respiratory Biomedical Research Unit, University of Leicester, Leicester, UK.
9
Department of Medicine, Imperial College London, London, UK.
10
Complement and Inflammation Research Section, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
11
Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
12
Departments of Biochemistry and Computer Science, Purdue University, West Lafayette, IN, USA.
13
MRC, Centre for Transplantation, King's College London, London, UK. behdad.afzali@nih.gov.
14
Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. behdad.afzali@nih.gov.
15
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. behdad.afzali@nih.gov.

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.

PMID:
30397350
PMCID:
PMC6474659
DOI:
10.1038/s41590-018-0230-z
[Indexed for MEDLINE]
Free PMC Article

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