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

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 is unknown. Here we use thermogenic adipose tissue from mice as a model system to show that T cells, specifically T cells, have a crucial role in promoting sympathetic innervation, at least in part by driving the expression of TGF1 in parenchymal cells via the IL-17 receptor complex (IL-17RC). Ablation of IL-17RC specifically in adipose tissue reduces expression of TGF1 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 TGF1 expression. Ablating cells and the IL-17RC signalling pathway also impairs sympathetic innervation in salivary glands and the lungs. These findings demonstrate coordination between T cells and parenchymal cells to regulate sympathetic innervation.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: mark Jedrychowski  

LAB HEAD: Bruce Spiegelman

PROVIDER: PXD017424 | Pride | 2020-03-02

REPOSITORIES: Pride