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

Citation:

Ayano C. Kohlgruber, Shani T. Gal-Oz, Nelson M. LaMarche, Moto Shimazaki, Danielle Duquette, Hung N. Nguyen, Amir I. Mina, Tyler Paras, Ali Tavakkoli, Ulrich von Andrian, Alexander S. Banks, Tal Shay, Michael B. Brenner, and Lydia Lynch. 2018. “γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis.” Nature ImmunologyNature Immunology, 19, Pp. 464-474.

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.