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.
Cell Metab. 2013 Mar 5;17(3):411-22. doi: 10.1016/j.cmet.2013.02.009.
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.
脂肪组织驻留 T 细胞（ARTs）调节肥胖中的代谢和炎症反应，但 ART 激活信号知之甚少。在这里，我们将 II 类主要组织相容性复合体（MHCII）描述为高脂肪饮食（HFD）诱导肥胖的重要组成部分。对原代脂肪细胞的微阵列分析显示，涉及 MHCII 抗原加工和呈递的多个基因在肥胖女性中增加。在小鼠中，脂肪细胞 MHCII 在 HFD 上的 2 周内增加，与促炎 ART 标志物的增加和抗炎 ART 标志物的减少平行，并先于脂肪组织巨噬细胞（ATM）积累和促炎 M1 极化。小鼠 3T3-L1 和原代脂肪细胞以抗原特异性、接触依赖性的方式激活 T 细胞，表明脂肪细胞 MHCII 具有功能。尽管 HFD 喂养的 MHCII（-/-）小鼠的肥胖程度与野生型小鼠相似，但它们发展出的脂肪炎症和胰岛素抵抗较少。这些研究揭示了一种机制，即涉及 MHCII 的 HFD 诱导的脂肪细胞/ART 对话引发脂肪炎症，并与 ATM MHCII 一起，使其进展加剧。
