Open Accessγδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis
Author(s) -
Bo Hu,
Chengcheng Jin,
Xing Zeng,
Jon M. Resch,
Mark P. Jedrychowski,
Zongfang Yang,
Bhav. Desai,
Alexander S. Banks,
Bradford B. Lowell,
Diane Mathis,
Bruce M. Spiegelman
Publication year - 2020
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-020-2028-z
Subject(s) - thermogenesis , sympathetic nervous system , adipose tissue , biology , sympathetic innervation , neurotrophin , microbiology and biotechnology , adipocyte , endocrinology , medicine , receptor , biochemistry , blood pressure
The sympathetic nervous system innervates peripheral organs to regulate their function and maintain homeostasis, whereas target cells also produce neurotrophic factors to promote sympathetic innervation 1,2 . 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.