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Nat Immunol. 2018 May;19(5):464-474. doi: 10.1038/s41590-018-0094-2. Epub 2018 Apr 18.

γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis.

Author information

1
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA.
2
Division of Medical Sciences, Harvard Medical School, Boston, MA, USA.
3
Department of Life Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
4
Division of Endocrinology, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
5
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia.
6
ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Australia.
7
Department of General and Gastrointestinal Surgery, Brigham and Women's Hospital, Boston, MA, USA.
8
Department of Microbiology and Immunology, Harvard Medical School, Boston, MA, USA.
9
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA. mbrenner@research.bwh.harvard.edu.
10
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA. llynch@bwh.harvard.edu.
11
Division of Endocrinology, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. llynch@bwh.harvard.edu.
12
School of Biochemistry and Immunology, Trinity College, Dublin, Ireland. llynch@bwh.harvard.edu.

Abstract

γδ T cells are situated at barrier sites and guard the body from infection and damage. However, little is known about their roles outside of host defense in nonbarrier tissues. Here, we characterize a highly enriched tissue-resident population of γδ T cells in adipose tissue that regulate age-dependent regulatory T cell (Treg) expansion and control core body temperature in response to environmental fluctuations. Mechanistically, innate PLZF+ γδ T cells produced tumor necrosis factor and interleukin (IL) 17 A and determined PDGFRα+ and Pdpn+ stromal-cell production of IL-33 in adipose tissue. Mice lacking γδ T cells or IL-17A exhibited decreases in both ST2+ Treg cells and IL-33 abundance in visceral adipose tissue. Remarkably, these mice also lacked the ability to regulate core body temperature at thermoneutrality and after cold challenge. Together, these findings uncover important physiological roles for resident γδ T cells in adipose tissue immune homeostasis and body-temperature control.

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PMID:
29670241
DOI:
10.1038/s41590-018-0094-2
[Indexed for MEDLINE]

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