γγ17 coordinate innervation of white adipose tissue 2335094

Abstract

Abstract Introduction Recent work from our lab shows that adipose tissue-resident γδ T cells produce homeostatic levels of interleukin (IL)-17 in a circadian rhythm, regulating of de novo lipogenesis. Innervation of adipose tissue promotes energy storage during caloric intake, utilizes energy stores during demand, and prevents activity when energy stores are low. IL-17 producing γδ T cell (γγ17) promote innervation of brown adipose tissue indirectly via adipocytes; however, it remains unknown whether IL-17 acts directly on neurons. This led us to ask whether IL-17 receptor signaling coordinates adipose tissue innervation to regulate whole-body metabolism. Methods White adipose tissue depots were isolated from wildtype (WT) or IL-17A/F KO mice. Flow cytometric analysis was used to characterize changes in the γδ T cell population. Whole adipose tissue depots were cleared using iDISCO and imaged via light sheet microscopy to map the nerve networks. Results We measured reduced volume of adipose tissue innervation in IL17 KO tissue as compared to control (p < 0.01). Interestingly, the adipose tissue of IL17 KO mice has 18% increase in the frequency of the Vγ6 subset of γγ17 (p < 0.001). In contrast, the inguinal lymph node has 15% reduction in the frequency of Vγ6 T cells (p < 0.0001). RNAseq analysis indicates that γγ17 are enriched for neuropeptide receptors. Conclusion Our results indicate that disrupting IL-17 signaling in adipose tissue results in reduced tissue innervation. Our changes in γγ17 frequency suggest that Vγ6 are recruited to the adipose in response to reduced innervation. The presence of neuropeptide receptors on γγ17 may provide a novel mechanism of neuroimmune crosstalk between neurons and γδ T cells. Funding Source n/a Topic Categories Neuroimmunology (NEUR)