Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Nature. 2020 Feb;578(7796):610-614. doi: 10.1038/s41586-020-2028-z. Epub 2020 Feb 19.
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.
交感神经系统支配外周器官以调节其功能并维持内稳态，而靶细胞也产生神经营养因子以促进交感神经支配。这种双向通讯的分子基础仍有待充分确定。在这里，我们使用来自小鼠的产热脂肪组织作为模型系统，表明 T 细胞，特别是 γδ T 细胞，在促进交感神经支配方面起着至关重要的作用，至少部分是通过通过白细胞介素 17 受体 C (IL-17RC) 在实质细胞中驱动 TGFβ1 的表达。特异性在脂肪组织中缺失 IL-17RC 会降低脂肪细胞中 TGFβ1 的表达，损害局部交感神经支配，并导致肥胖和其他与热生成缺陷一致的代谢表型；通过恢复 TGFβ1 的表达可以完全挽救神经支配。缺失 γδ Τ 细胞和 IL-17RC 信号通路也会损害唾液腺等其他组织中的交感神经支配。这些发现表明 T 细胞和实质细胞之间的协调调节交感神经支配。
