PLX254541

GSE144255: gdT cells and adipocyte IL-17RC control fat innervation and thermogenesis

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

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. The molecular basis of this bi-directional communication remains to be fully elucidated. We use thermogenic adipose tissue as a model system to show that T cells, specifically gdT cells, play a critical role in promoting sympathetic innervation, at least in part through driving TGF1 expression in parenchymal cells via IL-17 Receptor C. Adipose-specific ablation of IL-17 Receptor C reduces TGF1 expression in adipocytes, impairs local sympathetic innervation and causes obesity and other metabolic phenotypes consistent with defective thermogenesis; innervation can be fully rescued by restoring TGF1 expression. Ablating gdT cells and the IL-17 Receptor C signaling pathway also impairs sympathetic innervation in salivary glands and the lung. These findings demonstrate T cell/parenchymal cell coordination to regulate sympathetic innervation. SOURCE: Spiegelman LabBruce Spiegelman Dana Farber Cancer Institute