Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity
Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity
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脂肪组 1 先天淋巴细胞促进肥胖患者的脂肪组织纤维化和糖尿病
DOI：
10.1038/s41467-019-11270-1
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发表时间：
2019
影响因子：
16.6
通讯作者：
Bi Yan
中科院分区：
文献类型：
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作者：
Wang Hongdong;Shen Lei;Sun Xitai;Liu Fangcen;Feng Wenhuan;Jiang Chunping;Chu Xuehui;Ye Xiao;Jiang Can;Wang Yan;Zhang Pengzi;Zang Mengwei;Zhu Dalong;Bi Yan
肥胖导致2型糖尿病(T2D)的致病因素尚不完全清楚。第1组先天淋巴样细胞(ILC1s)是先天免疫的效应者，在炎症组织中富含。在这里，我们发现肥胖的T2D患者的脂肪ILC1s的数量增加，并与血糖参数和血液中的ILC1s的数量相关；循环ILC1s的数量减少是减肥手术后代谢改善的结果。体外共培养实验表明，人脂肪ILC1s促进脂肪纤维化形成和CD11c+巨噬细胞活化。过继转染法重建Prkdc−/−IL2RG−/−小鼠脂肪ILC1群可通过激活转化生长因子β1信号通路促进脂肪纤维化的发生，而转导−/−ILC1s对脂肪纤维化无影响。此外，使用IL-12中和抗体抑制ILC1s的脂肪积累可以减轻脂肪组织纤维化，提高血糖耐受性。我们的数据提供了对肥胖相关的T2D局部免疫紊乱机制的见解。
Pathogenic factors driving obesity to type 2 diabetes (T2D) are not fully understood. Group 1 innate lymphoid cells (ILC1s) are effectors of innate immunity and enriched in inflamed tissues. Here we show that the number of adipose ILC1s increases in obese T2D patients and correlates with glycemic parameters and with the number of ILC1s in the blood; circulating ILC1 numbers decrease as a result of metabolic improvements after bariatric surgery. In vitro co-culture experiments show that human adipose ILC1s promote adipose fibrogenesis and CD11c+macrophage activation. Reconstruction of the adipose ILC1 population inPrkdc−/−IL2rg−/−mice by adoptive transfer drives adipose fibrogenesis through activation of TGFβ1 signaling; however, transfer ofIfng−/−ILC1s has no effect on adipose fibrogenesis. Furthermore, inhibiting adipose accumulation of ILC1s using IL-12 neutralizing antibodies attenuates adipose tissue fibrosis and improves glycemic tolerance. Our data present insights into the mechanisms of local immune disturbances in obesity-related T2D.