@article{da61f29f9d4049e3b809aca57285cd5b,
title = "γδ 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 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.",
author = "Bo Hu and Chengcheng Jin and Xing Zeng and Resch, {Jon M.} and Jedrychowski, {Mark P.} and Zongfang Yang and Desai, {Bhavna N.} and Banks, {Alexander S.} and Lowell, {Bradford B.} and Diane Mathis and Spiegelman, {Bruce M.}",
note = "Funding Information: Acknowledgements We thank M. L. Mather, E. Maratos-Flier, R. Garrity, Z. Deng, A. Mina and D. Cabarkapa for help with CLAMS studies. We thank T. Jacks for his support and input for this project as C.J.{\textquoteright}s postdoctoral advisor. We thank S. L. Gaffen and Y. Iwakura for sharing the Il17f −/− mice, J. K. Kolls for the Il17rc fl/fl mice, and Amgen for the Il17rc −/− and Il17ra −/− mice. We thank A. Mann, N. Asinovski and K. Hattori for the Vγ6Vδ1 transgenic mice and the 17D1 antibody. We thank C. Zhao for help with the immunofluorescence staining and confocal imaging analysis; L. Kazak and E. T. Chounchani for help with the EMG study; and R. J. Akhurst and S. Basu for sharing mice. We thank the Nikon Imaging Center at Harvard Medical School for all imaging studies; the Rodent Histology Core at Harvard Medical School for histology studies; the viral core at Children{\textquoteright}s Hospital Boston for AAV production; and the Neurobiology Department and the Neurobiology Imaging Facility for consultation and instrument availability that supported this work. This facility is supported in part by the Neural Imaging Center as part of an NINDS P30 Core Center grant NS072030. We thank Z. Herbert, A. Caruso and members of the Molecular Biology Core Facilities at the Dana-Farber Cancer Institute for RNA-seq analysis. We thank the Flow Cytometry Core Facilities at the Swanson Biotechnology Center at MIT and the Dana-Farber Cancer Institute. We thank Y. Chen, D. Bogoslavsk, J. Szpyt and all members of the Spiegelman and Mathis laboratories for help and input in this project. B.H. is a Cancer Research Institute/Leonard Kahn Foundation Fellow. C.J. is supported by a K99 Award (CA226400) from the National Cancer Institute (NCI). This work was supported by grants to B.M.S. from the NIH DK 31405 and from the JPB Foundation. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2020",
month = feb,
day = "27",
doi = "10.1038/s41586-020-2028-z",
language = "English (US)",
volume = "578",
pages = "610--614",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7796",
}