γδT細胞和脂肪細胞調控脂肪神經支配和產熱
作者：
小柯機器人發布時間：2020/2/29 23:40:29
美國丹娜—法伯癌症研究所Bruce M. Spiegelman小組近日取得一項新成果。他們發現γδ T細胞和脂肪細胞IL-17RC調控脂肪神經支配和產熱。2020年2月19日出版的《自然》在線發表了這項成果。
研究人員利用小鼠產熱脂肪組織作為模型系統，發現T細胞（尤其是γδ T細胞）在促進交感神經支配方面發揮關鍵作用，至少部分是通過經由IL-17受體C（IL-17RC）驅動TGFβ1在實質細胞中表達來完成的。特別是在脂肪組織中IL-17RC缺失會降低脂肪細胞中TGFβ1的表達、損害局部交感神經、並導致肥胖和其他代謝表型，這與產熱不良的表型類似。
通過恢復TGFβ1的表達，神經支配可以得到完全挽救。γδ T細胞和IL-17RC信號同時缺失也損害了其他組織如唾液腺的交感神經。這些發現表明T細胞和實質細胞之間相協調以調控交感神經支配。
據悉，交感神經系統支配周圍器官以調節其功能並維持體內穩態，而靶細胞也產生神經營養因子以促進交感神經支配。人們尚不完全清楚這種雙向交流的分子基礎。
附：英文原文
Title: γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis
Author: Bo Hu, Chengcheng Jin, Xing Zeng, Jon M. Resch, Mark P. Jedrychowski, Zongfang Yang, Bhavna N. Desai, Alexander S. Banks, Bradford B. Lowell, Diane Mathis, Bruce M. Spiegelman
Issue&Volume: 2020-02-19
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.
DOI: 10.1038/s41586-020-2028-z
Source: https://www.nature.com/articles/s41586-020-2028-z