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γδ T 细胞产生白细胞介素-17A 调节脂肪组织调节性 T 细胞的动态平衡和产热。

γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis.

机构信息

Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA.

Division of Medical Sciences, Harvard Medical School, Boston, MA, USA.

出版信息

Nat Immunol. 2018 May;19(5):464-474. doi: 10.1038/s41590-018-0094-2. Epub 2018 Apr 18.

Abstract

γδ T cells are situated at barrier sites and guard the body from infection and damage. However, little is known about their roles outside of host defense in nonbarrier tissues. Here, we characterize a highly enriched tissue-resident population of γδ T cells in adipose tissue that regulate age-dependent regulatory T cell (T) expansion and control core body temperature in response to environmental fluctuations. Mechanistically, innate PLZF γδ T cells produced tumor necrosis factor and interleukin (IL) 17 A and determined PDGFRα and Pdpn stromal-cell production of IL-33 in adipose tissue. Mice lacking γδ T cells or IL-17A exhibited decreases in both ST2 T cells and IL-33 abundance in visceral adipose tissue. Remarkably, these mice also lacked the ability to regulate core body temperature at thermoneutrality and after cold challenge. Together, these findings uncover important physiological roles for resident γδ T cells in adipose tissue immune homeostasis and body-temperature control.

摘要

γδ T 细胞位于屏障部位,可防止身体受到感染和损伤。然而,人们对非屏障组织中它们在宿主防御以外的作用知之甚少。在这里,我们描述了脂肪组织中一种高度富集的组织驻留型 γδ T 细胞亚群,它可调节年龄依赖性调节性 T 细胞(T 细胞)的扩增,并响应环境波动来控制核心体温。在机制上,先天的 PLZF γδ T 细胞产生肿瘤坏死因子和白细胞介素(IL)17A,并决定脂肪组织中 PDGFRα 和 Pdpn 基质细胞产生 IL-33。缺乏 γδ T 细胞或 IL-17A 的小鼠,其内脏脂肪组织中 ST2 T 细胞和 IL-33 的丰度均降低。值得注意的是,这些小鼠也丧失了在体温中性和冷应激后调节核心体温的能力。总之,这些发现揭示了驻留 γδ T 细胞在脂肪组织免疫稳态和体温控制中的重要生理作用。

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