title: Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation.
abstract: 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.
authors.affiliation: The Methodist Diabetes and Metabolism Institute, Center for Diabetes Research and Center for Inflammation and Epigenetics, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX 77030, USA.
authors.forename: Tuo
authors.initials: T
authors.lastname: Deng
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lyon
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Minze
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lin
authors.forename: Jia
authors.initials: J
authors.lastname: Zou
authors.forename: Joey Z
authors.initials: JZ
authors.lastname: Liu
authors.forename: Yuelan
authors.initials: Y
authors.lastname: Ren
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yin
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Hamilton
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Reardon
authors.forename: Vadim
authors.initials: V
authors.lastname: Sherman
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Wang
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Phillips
authors.forename: Paul
authors.initials: P
authors.lastname: Webb
authors.forename: Stephen T C
authors.initials: ST
authors.lastname: Wong
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Wang
authors.forename: Willa A
authors.initials: WA
authors.lastname: Hsueh
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D009765:Obesity / Q000150:complications / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric