Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance

被引：258

作者：

O'Sullivan, Timothy E. ^{[1
]}

Rapp, Moritz ^{[1
]}

Fan, Xiying ^{[1
]}

Weizman, Orr-El ^{[1
]}

Bhardwaj, Priya ^{[2
]}

Adams, Nicholas M. ^{[1
]}

Walzer, Thierry ^{[3
]}

Dannenberg, Andrew J. ^{[2
]}

Sun, Joseph C. ^{[1
,4
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Immunol Program, New York, NY 10065 USA

[2] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA

[3] CIRI, F-69007 Lyon, France

[4] Weill Cornell Med Coll, Dept Immunol & Microbial Pathogenesis, New York, NY 10065 USA

来源：

IMMUNITY | 2016年 / 45卷 / 02期

关键词：

TISSUE MACROPHAGE INFILTRATION; NATURAL-KILLER-CELLS; DIET-INDUCED OBESITY; CD4(+) T-CELLS; CHRONIC INFLAMMATION; ADAPTIVE IMMUNITY; INTERFERON-GAMMA; NKT CELLS; HOMEOSTASIS; CANCER;

D O I：

10.1016/j.immuni.2016.06.016

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：

Innate lymphoid cells (ILCs) function to protect epithelial barriers against pathogens and maintain tissue homeostasis in both barrier and non-barrier tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease. Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but phenotypically and functionally distinct from adipose mature natural killer (NK) and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s maintained long-term tissue residency. Diet-induced obesity drove early production of interleukin (IL)-12 in adipose tissue depots and led to the selective proliferation and accumulation of adipose-resident ILC1s in a manner dependent on the IL-12 receptor and STAT4. ILC1-derived interferon-g was necessary and sufficient to drive proinflammatory macrophage polarization to promote obesity-associated insulin resistance. Thus, adipose-resident ILC1s contribute to obesity-related pathology in response to dysregulated local proinflammatory cytokine production.

引用

页码：428 / 441

页数：14

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