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

Ayano C Kohlgruber; Shani T Gal-Oz; Nelson M LaMarche; Moto Shimazaki; Danielle Duquette; Hui-Fern Koay; Hung N Nguyen; Amir I Mina; Tyler Paras; Ali Tavakkoli; Ulrich von Andrian; Adam P Uldrich; Dale I Godfrey; Alexander S Banks; Tal Shay; Michael B Brenner; Lydia Lynch

doi:10.1038/s41590-018-0094-2

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

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

Authors

Ayano C Kohlgruber^{1

2}, Shani T Gal-Oz³, Nelson M LaMarche^{1

2}, Moto Shimazaki¹, Danielle Duquette⁴, Hui-Fern Koay^{5

6}, Hung N Nguyen¹, Amir I Mina⁴, Tyler Paras¹, Ali Tavakkoli⁷, Ulrich von Andrian^{2

8}, Adam P Uldrich^{5

6}, Dale I Godfrey^{5

6}, Alexander S Banks⁴, Tal Shay³, Michael B Brenner⁹, Lydia Lynch^{10

11

12}

Affiliations

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. [email protected].
¹⁰ Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA. [email protected].
¹¹ Division of Endocrinology, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. [email protected].
¹² School of Biochemistry and Immunology, Trinity College, Dublin, Ireland. [email protected].

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 (T_reg) 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⁺ T_reg 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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / cytology*
Adipose Tissue / physiology
Animals
Homeostasis / physiology*
Humans
Interleukin-17 / metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Antigen, T-Cell, gamma-delta
T-Lymphocyte Subsets / physiology
T-Lymphocytes, Regulatory / physiology*
Thermogenesis / physiology*

Substances

Interleukin-17
Receptors, Antigen, T-Cell, gamma-delta

Abstract

Publication types

MeSH terms

Substances

Grants and funding