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

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) 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 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.

IL ‐7‐dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti‐tumour response

“…Consistent with previous reports, Vγ4 + and Vγ6 + γδ17 T cells expressed Ccr2, Ccr6 , Il7r and Il23r at a higher level and down‐regulated expression of Cd27 and Sell . Master transcription factors were highly expressed in the respective lineage: Rorc , Sox13 , Maf and Zbtab16 in γδ17 T cells and Eomes , Tbx21 and Id3 in γδ1 T cells . In homeostasis, γδ1 T cells expressed higher levels of Ifng and γδ17 T cells sporadically expressed Il17a .…”

An update on immune dysregulation in obesity‐related insulin resistance

“…Gamma delta T (γδ T) cells are innate‐like lymphocytes that frequently express the transcription factor PLZF and are classified based on the expression of the costimulatory receptor CD27. Those who are CD27 + (γδ27 + ) express T‐bet and produce IFN‐γ but CD27 − (γδ27 − /γδ17) cells express ROR‐γt and produce IL‐17 . γδ T cells constitute ~25% of the AT‐T cells in which most of them are γδ17 and their numbers are increased during obesity .…”

Meningeal γδ T cell–derived IL-17 controls synaptic plasticity and short-term memory

“…In stark contrast with their pathogenic role in neuroinflammation, γδ17 T cells are known to constitute a major source of IL-17 in various other non-lymphoid tissues at steady state, which interestingly contributes to normal tissue physiology, as illustrated by recent works reporting their key functions in bone repair (14) and thermogenesis (15). This is an interesting nascent field that may reveal novel physiological roles for γδ17 T cells residing in other tissues.…”