Class II Major Histocompatibility Complex Plays an Essential Role in Obesity-Induced Adipose Inflammation

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• 作者：Tuo Deng¹ ; Christopher J. Lyon¹ ; Laurie J. Minze¹ ; Jianxin Lin¹ ; Jia Zou¹ ; Joey Z. Liu¹ ; Yuelan Ren¹ ; Zheng Yin² ; Dale J. Hamilton¹ ; Patrick R. Reardon³ ; Vadim Sherman³ ; Helen Y. Wang¹ ; Kevin J. Phillips¹ ; Paul Webb¹ ; Stephen T.C. Wong² ; Rong-fu Wang¹ ; Willa A. Hsueh¹ ; ^{wahsueh@tmhs.org}
• 刊名：Cell Metabolism
• 出版年：2013
• 出版时间：5 March, 2013
• 年：2013
• 卷：17
• 期：3
• 页码：411-422
• 全文大小：1158 K

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class=""h3"">Summary

Adipose-resident T?cells (ARTs) regulate metabolic and inflammatory responses in obesity, but ART activation signals are poorly understood. Here, we describe class II major histocompatibility complex (MHCII) as an important component of high-fat-diet?(HFD)-induced obesity. Microarray analysis of primary adipocytes revealed that multiple genes involved in MHCII antigen processing and presentation increased in obese women. In mice, adipocyte MHCII increased within 2?weeks on HFD, paralleling increases in proinflammatory ART markers and decreases in anti-inflammatory ART markers, and preceding adipose tissue macrophage (ATM) accumulation and proinflammatory M1 polarization. Mouse 3T3-L1 and primary adipocytes activated T?cells in an antigen-specific, contact-dependent manner, indicating that adipocyte MHCII is functional. HFD-fed MHCII^?/? mice developed less adipose inflammation and insulin resistance than did wild-type mice, despite developing similar adiposity. These investigations uncover a mechanism whereby a HFD-induced adipocyte/ART dialog involving MHCII instigates adipose inflammation and, together with ATM MHCII, escalates its progression.