Institute of Anatomy, Leipzig University, Leipzig, D-04103, Germany.
Institute of Anatomy and Cell Biology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), D-06108, Germany.
Eur J Immunol. 2021 Jun;51(6):1399-1411. doi: 10.1002/eji.202048870. Epub 2021 May 4.
Obesity is frequently associated with a chronic low-grade inflammation in the adipose tissue (AT) and impaired glucose homeostasis. Adipose tissue macrophages (ATMs) have been shown to accumulate in the inflamed AT either by means of recruitment from the blood or local proliferation. ATM proliferation and activation can be stimulated by TH2 cytokines, such as IL-4 and IL-13, suggesting involvement of CD4-positive T cells in ATM proliferation and activation. Furthermore, several studies have associated T cells to alterations in glucose metabolism. Therefore, we sought to examine a direct impact of CD4-positive T cells on ATM activation, ATM proliferation and glucose homeostasis using an in vivo depletion model. Surprisingly, CD4 depletion did not affect ATM activation, ATM proliferation, or insulin sensitivity. However, CD4 depletion led to a significant improvement of glucose tolerance. In line with this, we found moderate disturbances in pancreatic endocrine function following CD4 depletion. Hence, our data suggest that the effect on glucose metabolism observed after CD4 depletion might be mediated by organs other than AT and independent of AT inflammation.
肥胖常伴有脂肪组织（AT）的慢性低度炎症和葡萄糖稳态受损。已经表明，脂肪组织巨噬细胞（ATMs）可以通过从血液中募集或局部增殖来积累在炎症的 AT 中。TH2 细胞因子，如 IL-4 和 IL-13，可以刺激 ATM 增殖和激活，这表明 CD4 阳性 T 细胞参与了 ATM 增殖和激活。此外，几项研究已经将 T 细胞与葡萄糖代谢的改变联系起来。因此，我们试图使用体内耗竭模型来检查 CD4 阳性 T 细胞对 ATM 激活、ATM 增殖和葡萄糖稳态的直接影响。令人惊讶的是，CD4 耗竭并不影响 ATM 激活、ATM 增殖或胰岛素敏感性。然而，CD4 耗竭导致葡萄糖耐量显著改善。与此一致的是，我们发现 CD4 耗竭后胰腺内分泌功能有中度紊乱。因此，我们的数据表明，CD4 耗竭后观察到的葡萄糖代谢的影响可能是由 AT 以外的器官介导的，并且与 AT 炎症无关。
