Journal article
γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis
Nature (London), Vol.578(7796), pp.610-614
02/2020
DOI: 10.1038/s41586-020-2028-z
PMCID: PMC7055484
PMID: 32076265
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 innervation
. 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.
Details
- Title: Subtitle
- γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis
- Creators
- Bo Hu - Department of Cell Biology, Harvard Medical School, Boston, MA, USAChengcheng Jin - Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USAXing Zeng - Department of Cell Biology, Harvard Medical School, Boston, MA, USAJon M Resch - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USAMark P Jedrychowski - Department of Cell Biology, Harvard Medical School, Boston, MA, USAZongfang Yang - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USABhavna N Desai - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USAAlexander S Banks - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USABradford B Lowell - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USADiane Mathis - Department of Immunology, Harvard Medical School, Boston, MA, USABruce M Spiegelman - Department of Cell Biology, Harvard Medical School, Boston, MA, USA. bruce_spiegelman@dfci.harvard.edu
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.578(7796), pp.610-614
- DOI
- 10.1038/s41586-020-2028-z
- PMID
- 32076265
- PMCID
- PMC7055484
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Publisher
- England
- Grant note
- R01 DK031405 / NIDDK NIH HHS K99 CA226400 / NCI NIH HHS R01 DK092541 / NIDDK NIH HHS R37 DK031405 / NIDDK NIH HHS R00 CA226400 / NCI NIH HHS P30 NS072030 / NINDS NIH HHS
- Language
- English
- Date published
- 02/2020
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984065749802771
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