Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Adv Exp Med Biol. 2021;1278:125-139. doi: 10.1007/978-981-15-6407-9_8.
Obesity dramatically increases the risk of numerous conditions, including type 2 diabetes mellitus and other components of the metabolic syndrome. Pro-inflammatory changes that occur in adipose tissue are critical to the pathogenesis of these obesity-induced complications. Adipose tissue is one of the body's largest endocrine organs, and the cells that comprise the adipose tissue immunoenvironment secrete multiple factors (including adipokines and cytokines) that impact systemic metabolism. In particular, immunosuppressive regulatory T cells (Tregs) decline in obesity, partly in response to its complex interaction with adipocytes, and this decline contributes to disruption of the typical homeostasis observed in lean adipose tissue. Although the regulation of Treg differentiation, function, and enrichment is incompletely understood, factors including various cell-surface co-stimulatory molecules, certain lipid species, and cytokines such as PPARγ, adiponectin, and leptin are important mediators. It is also clear that there may be depot-specific differences in Tregs, rendering adipose tissue Tregs distinct from lymphoid or circulating Tregs, with implications on maintenance and functionality. While most of these findings are derived from studies in murine models, comparatively little is known about the human adipose tissue Treg signature, which requires further investigation.
肥胖显著增加了多种疾病的风险，包括 2 型糖尿病和代谢综合征的其他组成部分。脂肪组织中发生的促炎变化对这些肥胖引起的并发症的发病机制至关重要。脂肪组织是人体最大的内分泌器官之一，组成脂肪组织免疫环境的细胞分泌多种影响全身代谢的因子（包括脂肪因子和细胞因子）。特别是，免疫抑制性调节性 T 细胞（Tregs）在肥胖中减少，部分原因是它与脂肪细胞的复杂相互作用，这种减少导致了在瘦脂肪组织中观察到的典型平衡的破坏。尽管 Treg 分化、功能和富集的调节尚不完全清楚，但包括各种细胞表面共刺激分子、某些脂质种类以及细胞因子（如 PPARγ、脂联素和瘦素）在内的因素是重要的调节因子。显然，Tregs 可能存在特定脂肪库的差异，使脂肪组织 Tregs 有别于淋巴样或循环 Tregs，这对维持和功能有影响。虽然这些发现大多来自于对鼠模型的研究，但关于人类脂肪组织 Treg 特征的了解相对较少，这需要进一步研究。
