Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity

被引：235

作者：

Lee, Byung-Cheol ^{[1
,2
,3
]}

Kim, Myung-Sunny ^{[1
,2
,4
,5
]}

Pae, Munkyong ^{[1
,2
,7
]}

Yamamoto, Yasuhiko ^{[1
,2
]}

Eberle, Delphine ^{[1
,2
,8
]}

Shimada, Takeshi ^{[1
,2
]}

Kamei, Nozomu ^{[1
,2
]}

Park, Hee-Sook ^{[4
,5
]}

Sasorith, Souphatta ^{[1
,2
]}

Woo, Ju Rang ^{[1
,2
]}

You, Jia ^{[1
,2
]}

Mosher, William ^{[1
,2
]}

Brady, Hugh J. M. ^{[6
]}

Shoelson, Steven E. ^{[1
,2
]}

Lee, Jongsoon ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA

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

[3] Kyung Hee Univ, Coll Korean Med, Dept Internal Med, Seoul 130701, South Korea

[4] Korea Food Res Inst, Songnam 463746, South Korea

[5] UST, Songnam 463746, South Korea

[6] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, South Kensington Campus, London SW7 2AZ, England

[7] Chungbuk Natl Univ, Dept Food & Nutr, Cheongju 361763, South Korea

[8] Univ Lille, CHRU Lille, EA Environm Perinatal & Sante 4489, F-59000 Lille, France

来源：

CELL METABOLISM | 2016年 / 23卷 / 04期

关键词：

NECROSIS-FACTOR-ALPHA; T-CELLS; NK CELLS; IMMUNE-RESPONSE; INFLAMMATION; SUBSETS; E4BP4; ACCUMULATION; HOMEOSTASIS; ACTIVATION;

D O I：

10.1016/j.cmet.2016.03.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Obesity-induced inflammation mediated by immune cells in adipose tissue appears to participate in the pathogenesis of insulin resistance. We show that natural killer (NK) cells in adipose tissue play an important role. High-fat diet (HFD) increases NK cell numbers and the production of proinflammatory cytokines, notably TNF alpha, in epididymal, but not subcutaneous, fat depots. When NK cells were depleted either with neutralizing antibodies or genetic ablation in E4bp4(+/-) mice, obesity-induced insulin resistance improved in parallel with decreases in both adipose tissue macrophage (ATM) numbers, and ATM and adipose tissue inflammation. Conversely, expansion of NK cells following IL-15 administration or reconstitution of NK cells into E4bp4(-/-) mice increased both ATM numbers and adipose tissue inflammation and exacerbated HFD-induced insulin resistance. These results indicate that adipose NK cells control ATMs as an upstream regulator potentially by producing proinflammatory mediators, including TNF alpha, and thereby contribute to the development of obesity-induced insulin resistance.

引用

页码：685 / 698

页数：14

共 45 条

[1] Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity [J].