Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity

被引：178

作者：

Boulenouar, Selma ^{[1
,2
]}

Michelet, Xavier ^{[1
,2
]}

Duquette, Danielle ^{[1
]}

Alvarez, David ^{[2
]}

Hogan, Andrew E. ^{[3
]}

Dold, Christina ^{[4
]}

O'Connor, Donal ^{[3
]}

Stutte, Suzanne ^{[2
]}

Tavakkoli, Ali ^{[1
]}

Winters, Desmond ^{[3
]}

Exley, Mark A. ^{[1
]}

O'Shea, Donal ^{[3
]}

Brenner, Michael B. ^{[1
]}

von Andrian, Ulrich ^{[2
]}

Lynch, Lydia ^{[1
,2
,4
]}

机构：

[1] Brigham & Womens Hosp, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] St Vincents Univ Hosp, Educ Res Ctr, Dublin 4, Ireland

[4] Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin 2, Ireland

来源：

IMMUNITY | 2017年 / 46卷 / 02期

基金：

欧洲研究理事会;

关键词：

NATURAL-KILLER-CELLS; INVARIANT NKT CELLS; T-CELLS; TISSUE MACROPHAGES; OBESITY; DIFFERENTIATION; DIVERSITY; PROMOTE; LIVER; BET;

D O I：

10.1016/j.immuni.2017.01.008

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Adipose tissue has a dynamic immune system that adapts to changes in diet and maintains homeostatic tissue remodeling. Adipose type 1 innate lymphoid cells (AT1-ILCs) promote pro-inflammatory macrophages in obesity, but little is known about their functions at steady state. Here we found that human and murine adipose tissue harbor heterogeneous populations of AT1-ILCs. Experiments using parabiotic mice fed a high-fat diet (HFD) showed differential trafficking of AT1-ILCs, particularly in response to short-and long-term HFD and diet restriction. At steady state, AT1-ILCs displayed cytotoxic activity toward adipose tissue macrophages (ATMs). Depletion of AT1-ILCs and perforin deficiency resulted in alterations in the ratio of inflammatory to anti-inflammatory ATMs, and adoptive transfer of AT1-ILCs exacerbated metabolic disorder. Diet-induced obesity impaired AT1-ILC killing ability. Our findings reveal a role for AT1-ILCs in regulating ATM homeostasis through cytotoxicity and suggest that this function is relevant in both homeostasis and metabolic disease.

引用

页码：273 / 286

页数：14

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