William Harvey Research Institute, Barts, and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Cell Metab. 2018 Mar 6;27(3):588-601.e4. doi: 10.1016/j.cmet.2018.02.007.
Visceral adipose tissue (VAT) has multiple roles in orchestrating whole-body energy homeostasis. In addition, VAT is now considered an immune site harboring an array of innate and adaptive immune cells with a direct role in immune surveillance and host defense. We report that conventional dendritic cells (cDCs) in VAT acquire a tolerogenic phenotype through upregulation of pathways involved in adipocyte differentiation. While activation of the Wnt/β-catenin pathway in cDC1 DCs induces IL-10 production, upregulation of the PPARγ pathway in cDC2 DCs directly suppresses their activation. Combined, they promote an anti-inflammatory milieu in vivo delaying the onset of obesity-induced chronic inflammation and insulin resistance. Under long-term over-nutrition, changes in adipocyte biology curtail β-catenin and PPARγ activation, contributing to VAT inflammation.
内脏脂肪组织（VAT）在调节全身能量平衡方面具有多种作用。此外，VAT 现在被认为是一个免疫部位，拥有一系列先天和适应性免疫细胞，它们在免疫监视和宿主防御中发挥直接作用。我们报告称，VAT 中的常规树突状细胞（cDC）通过上调参与脂肪细胞分化的途径获得耐受表型。虽然 cDC1 细胞中 Wnt/β-catenin 途径的激活诱导 IL-10 的产生，而 cDC2 细胞中 PPARγ 途径的上调直接抑制其激活。它们共同促进体内抗炎微环境，延缓肥胖引起的慢性炎症和胰岛素抵抗的发生。在长期过度营养的情况下，脂肪细胞生物学的变化会限制β-catenin 和 PPARγ 的激活，导致 VAT 炎症。
