National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China.
Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States.
Front Immunol. 2021 Jul 30;12:702955. doi: 10.3389/fimmu.2021.702955. eCollection 2021.
Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of insulin-producing β cells. T cells in CD4 T cell receptor transgenic Non-Obese Diabetic (NOD) mice ( NOD mice) can abruptly invade the pancreatic islets resulting in severe insulitis that progresses rapidly but rarely leads to spontaneous diabetes. This prevention of diabetes is mediated by T regulatory (Treg) cells in these mice. In this study, we investigated the role of interleukin 10 (IL-10) in the inhibition of diabetes in NOD mice by generating -deficient NOD mice ( NOD mice). Our results showed that NOD mice displayed robust and accelerated diabetes development. deficiency in NOD mice promoted the generation of neutrophils in the bone marrow and increased the proportions of neutrophils in the periphery (blood, spleen, and islets), accompanied by altered intestinal immunity and gut microbiota composition. studies showed that the gut microbiota from NOD mice can expand neutrophil populations. Moreover, studies demonstrated that the depletion of endogenous gut microbiota by antibiotic treatment decreased the proportion of neutrophils. Although deficiency in NOD mice had no obvious effects on the proportion and function of Treg cells, it affected the immune response and activation of CD4 T cells. Moreover, the pathogenicity of CD4 T cells was much increased, and this significantly accelerated the development of diabetes when these CD4 T cells were transferred into immune-deficient NOD mice. Our study provides novel insights into the role of IL-10 in the modulation of neutrophils and CD4 T cells in NOD mice, and suggests important crosstalk between gut microbiota and neutrophils in type 1 diabetes development.
1 型糖尿病是一种由 T 细胞介导的胰岛素产生β细胞破坏引起的自身免疫性疾病。在 CD4 T 细胞受体转基因非肥胖型糖尿病（NOD）小鼠（NOD 小鼠）中，T 细胞可以突然侵袭胰岛，导致严重的胰岛炎，这种炎症迅速进展，但很少导致自发性糖尿病。这种糖尿病的预防是由这些小鼠中的调节性 T 细胞（Treg 细胞）介导的。在这项研究中，我们通过生成白细胞介素 10（IL-10）缺陷型 NOD 小鼠（NOD 小鼠），研究了 IL-10 在 NOD 小鼠糖尿病抑制中的作用。我们的结果表明，NOD 小鼠表现出强烈且加速的糖尿病发展。NOD 小鼠中的 IL-10 缺乏促进了骨髓中中性粒细胞的生成，并增加了外周血、脾脏和胰岛中的中性粒细胞比例，同时改变了肠道免疫和肠道微生物群落组成。研究表明，NOD 小鼠的肠道微生物群落可以扩增中性粒细胞群体。此外，研究表明，抗生素处理耗尽内源性肠道微生物群会降低中性粒细胞的比例。虽然 NOD 小鼠中的 IL-10 缺乏对 Treg 细胞的比例和功能没有明显影响，但它影响了 CD4 T 细胞的免疫反应和激活。此外，CD4 T 细胞的致病性大大增加，当这些 CD4 T 细胞被转移到免疫缺陷型 NOD 小鼠中时，糖尿病的发展明显加速。我们的研究提供了关于 IL-10 在 NOD 小鼠中性粒细胞和 CD4 T 细胞调节中的作用的新见解，并提示肠道微生物群和中性粒细胞在 1 型糖尿病发展中存在重要的串扰。
