γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis

Bo Hu, Chengcheng Jin, Xing Zeng, Jon M. Resch, Mark P. Jedrychowski, Zongfang Yang, Bhavna N. Desai, Alexander S. Banks, Bradford B. Lowell, Diane Mathis, Bruce M. Spiegelman

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The sympathetic nervous system innervates peripheral organs to regulate their function and maintain homeostasis, whereas target cells also produce neurotrophic factors to promote sympathetic innervation1,2. The molecular basis of this bi-directional communication remains to be fully determined. Here we use thermogenic adipose tissue from mice as a model system to show that T cells, specifically γδ T cells, have a crucial role in promoting sympathetic innervation, at least in part by driving the expression of TGFβ1 in parenchymal cells via the IL-17 receptor C (IL-17RC). Ablation of IL-17RC specifically in adipose tissue reduces expression of TGFβ1 in adipocytes, impairs local sympathetic innervation and causes obesity and other metabolic phenotypes that are consistent with defective thermogenesis; innervation can be fully rescued by restoring TGFβ1 expression. Ablating γδ Τ cells and the IL-17RC signalling pathway also impairs sympathetic innervation in other tissues such as salivary glands. These findings demonstrate coordination between T cells and parenchymal cells to regulate sympathetic innervation.

Original languageEnglish (US)
Pages (from-to)610-614
Number of pages5
JournalNature
Volume578
Issue number7796
DOIs
StatePublished - Feb 27 2020
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis'. Together they form a unique fingerprint.

Cite this