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 and Bruce M. Spiegelman ()
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Bo Hu: Dana-Farber Cancer Institute
Chengcheng Jin: Massachusetts Institute of Technology
Xing Zeng: Dana-Farber Cancer Institute
Jon M. Resch: Beth Israel Deaconess Medical Center, Harvard Medical School
Mark P. Jedrychowski: Dana-Farber Cancer Institute
Zongfang Yang: Beth Israel Deaconess Medical Center, Harvard Medical School
Bhavna N. Desai: Beth Israel Deaconess Medical Center, Harvard Medical School
Alexander S. Banks: Beth Israel Deaconess Medical Center, Harvard Medical School
Bradford B. Lowell: Beth Israel Deaconess Medical Center, Harvard Medical School
Diane Mathis: Harvard Medical School
Bruce M. Spiegelman: Dana-Farber Cancer Institute

Nature, 2020, vol. 578, issue 7796, 610-614

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41586-020-2028-z

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