γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis
γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis
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DOI：
10.1038/s41586-020-2028-z
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发表时间：
2020-02-19
期刊：
影响因子：
64.8
通讯作者：
Spiegelman, Bruce M.
中科院分区：
文献类型：
--
作者：
Hu, Bo;Jin, Chengcheng;Spiegelman, Bruce M.
V-Gamma 6(+)V-Delta 1(+)γ-Delta T细胞通过激活脂肪细胞IL-17RC和促进交感神经支配小鼠的致热脂肪组织来控制耐冷性。交感神经系统支配周围器官调节其功能并维持内稳态，而靶细胞也产生神经营养因子促进交感神经支配(1，2)。这种双向通讯的分子基础仍有待完全确定。在这里，我们使用小鼠的致热脂肪组织作为一个模型系统，以表明T细胞，特别是Gamma Delta T细胞，在促进交感神经支配方面具有关键作用，至少部分是通过IL-17受体C(IL-17RC)驱动实质细胞中转化生长因子β1的表达。在脂肪组织中特异性地去除IL-17RC可减少脂肪细胞中转化生长因子β1的表达，损害局部交感神经支配，并导致肥胖等与产热缺陷相一致的代谢表型；恢复转化生长因子β1的表达可完全挽救神经支配。去除Gamma Delta tau细胞和IL-17RC信号通路也会损害其他组织的交感神经支配，如唾液腺。这些发现证明了T细胞和实质细胞之间的协调来调节交感神经。
V gamma 6(+) V delta 1(+) gamma delta T cells control tolerance to cold by activating adipocyte IL-17RC and promoting sympathetic innervation of thermogenic adipose tissue in mice.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(1,2). 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 gamma delta T cells, have a crucial role in promoting sympathetic innervation, at least in part by driving the expression of TGF beta 1 in parenchymal cells via the IL-17 receptor C (IL-17RC). Ablation of IL-17RC specifically in adipose tissue reduces expression of TGF beta 1 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 TGF beta 1 expression. Ablating gamma delta tau 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.