Université de Nice-Sophia Antipolis, Faculté de Médecine, Nice, France.
Diabetes. 2012 Sep;61(9):2238-47. doi: 10.2337/db11-1274. Epub 2012 May 17.
T-cell regulation in adipose tissue provides a link between inflammation and insulin resistance. Because of alterations in adipose tissue T-cell composition in obesity, we aimed to identify the antigen-presenting cells in adipose tissue of obese mice and patients with insulin resistance. Dendritic cells (DCs) and T cells were studied in mice and in two cohorts of obese patients. In lean mice, only CD11c(+) DCs were detected in adipose tissue. Adoptive transfer of naive CD4(+) T cells in Rag1(-/-) mice led to a predominant Th1 response in adipose tissue. In contrast, during obesity DCs (human CD11c(+)CD1c(+) and mouse CD11c(high)F4/80(low)) accumulated in adipose tissue. CD11c(high)F4/80(low) DCs from obese mice induced Th17 differentiation. In patients, the presence of CD11c(+)CD1c(+) DCs correlated with the BMI and with an elevation in Th17 cells. In addition, these DCs led to ex vivo Th17 differentiation. CD1c gene expression further correlated with homeostatic model assessment-insulin resistance in the subcutaneous adipose tissue of obese patients. We show for the first time the presence and accumulation of specific DCs in adipose tissue in mouse and human obesity. These DCs were functional and could be important regulators of adipose tissue inflammation by regulating the switch toward Th17 cell responses in obesity-associated insulin resistance.
脂肪组织中的 T 细胞调节提供了炎症和胰岛素抵抗之间的联系。由于肥胖症患者脂肪组织 T 细胞组成的改变，我们旨在鉴定肥胖症小鼠和胰岛素抵抗患者脂肪组织中的抗原呈递细胞。在小鼠和两组肥胖患者中研究了树突状细胞 (DC) 和 T 细胞。在瘦小鼠中，仅在脂肪组织中检测到 CD11c(+) DC。在 Rag1(-/-) 小鼠中过继转移幼稚 CD4(+) T 细胞导致脂肪组织中主要出现 Th1 反应。相比之下，在肥胖期间，DC(人 CD11c(+)CD1c(+)和鼠 CD11c(high)F4/80(low))在脂肪组织中积累。来自肥胖小鼠的 CD11c(high)F4/80(low) DC 诱导 Th17 分化。在患者中，CD11c(+)CD1c(+) DC 的存在与 BMI 以及 Th17 细胞的升高相关。此外，这些 DC 导致体外 Th17 分化。CD1c 基因表达进一步与肥胖患者皮下脂肪组织中稳态模型评估-胰岛素抵抗相关。我们首次在肥胖症的小鼠和人类脂肪组织中显示了特定 DC 的存在和积累。这些 DC 是功能性的，通过调节肥胖相关胰岛素抵抗中向 Th17 细胞反应的转变，可能是脂肪组织炎症的重要调节因子。
