Depletion of fat-resident Treg cells prevents age-associated insulin resistance

被引：283

作者：

Bapat, Sagar P. ^{[1
,2
]}

Suh, Jae Myoung ^{[2
,3
]}

Fang, Sungsoon ^{[2
,4
]}

Liu, Sihao ^{[2
]}

Zhang, Yang ^{[1
]}

Cheng, Albert ^{[1
]}

Zhou, Carmen ^{[1
]}

Liang, Yuqiong ^{[1
]}

LeBlanc, Mathias ^{[2
]}

Liddle, Christopher ^{[5
]}

Atkins, Annette R. ^{[2
]}

Yu, Ruth T. ^{[2
]}

Downes, Michael ^{[2
]}

Evans, Ronald M. ^{[2
,6
]}

Zheng, Ye ^{[1
]}

机构：

[1] Salk Inst Biol Studies, Immunobiol & Microbial Pathogenesis Lab, La Jolla, CA 92037 USA

[2] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA

[3] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon 34141, South Korea

[4] Sejong Univ, Dept Biotechnol, Coll Life Sci, Seoul 143747, South Korea

[5] Univ Sydney, Sydney Med Sch, Westmead Millennium Inst, Storr Liver Ctr, Sydney, NSW 2145, Australia

[6] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA

来源：

NATURE | 2015年 / 528卷 / 7580期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

VISCERAL ADIPOSE-TISSUE; RNA-SEQ; ORCHESTRATE DEVELOPMENT; PPAR-GAMMA; BEIGE FAT; MACROPHAGES; OBESITY; INFLAMMATION; DIFFERENTIATION; ACCUMULATION;

D O I：

10.1038/nature16151

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Age-associated insulin resistance (IR) and obesity-associated IR are two physiologically distinct forms of adult-onset diabetes. While macrophage-driven inflammation is a core driver of obesity-associated IR1-6, the underlying mechanisms of the obesity-independent yet highly prevalent age-associated IR7 are largely unexplored. Here we show, using comparative adipo-immune profiling in mice, that fat-resident regulatory T cells, termed fT(reg) cells, accumulate in adipose tissue as a function of age, but not obesity. Supporting the existence of two distinct mechanisms underlying IR, mice deficient in fT(reg) cells are protected against age-associated IR, yet remain susceptible to obesity-associated IR and metabolic disease. By contrast, selective depletion of fT(reg) cells via anti-ST2 antibody treatment increases adipose tissue insulin sensitivity. These findings establish that distinct immune cell populations within adipose tissue underlie ageing- and obesity-associated IR, and implicate fT(reg) cells as adipo-immune drivers and potential therapeutic targets in the treatment of age-associated IR.

引用

页码：137 / +

页数：17

共 36 条

[1]

[Anonymous], 2014, National Diabetes Statistics Report

[2]

Adipocyte Inflammation Is Essential for Healthy Adipose Tissue Expansion and Remodeling [J].