IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice.
IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice.
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DOI：
10.3389/fimmu.2021.702955
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wen L
中科院分区：
文献类型：
--
作者：
Huang J;Tan Q;Tai N;Pearson JA;Li Y;Chao C;Zhang L;Peng J;Xing Y;Zhang L;Hu Y;Zhou Z;Wong FS;Wen L
1型糖尿病是一种自身免疫性疾病，由T细胞介导的对产生胰岛素的β细胞的破坏引起。BDC2.5 CD 4 + T细胞受体转基因非肥胖糖尿病（NOD）小鼠（BDC2.5 + NOD小鼠）中的BDC2.5 T细胞可突然侵入胰岛，导致严重的胰岛炎，其迅速进展，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T调节性（Treg）细胞介导的。在这项研究中，我们研究了白细胞介素10（IL-10）在抑制糖尿病的BDC2.5 + NOD小鼠（BDC2.5 + IL-10 -/- NOD小鼠）中的作用，通过产生IL-10缺陷的BDC2.5 + NOD小鼠。我们的结果表明，BDC2.5 + IL-10 -/- NOD小鼠显示出稳健和加速的糖尿病发展。IL-10缺乏症在BDC2.5 + NOD小鼠中促进了骨髓中中性粒细胞的产生，并增加了外周（血液、脾脏和胰岛）中中性粒细胞的比例，伴随着肠道免疫和肠道微生物群组成的改变。体外研究表明，来自BDC2.5 + IL-10 -/- NOD小鼠的肠道微生物群可以扩增嗜中性粒细胞群体。此外，体内研究表明，通过抗生素治疗消耗内源性肠道微生物群降低了中性粒细胞的比例。IL-10缺乏对BD 2.5 + NOD小鼠Treg细胞的比例和功能无明显影响，但对CD 4 + T细胞的免疫应答和活化有影响。此外，CD 4 + T细胞的致病性大大增加，当这些CD 4 + T细胞被转移到免疫缺陷NOD小鼠时，这显著加速了糖尿病的发展。我们的研究为IL-10在调节BDC2.5 + NOD小鼠中性粒细胞和CD 4 + T细胞中的作用提供了新的见解，并表明肠道微生物群和中性粒细胞在1型糖尿病发展中的重要串扰。
Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of insulin-producing β cells. BDC2.5 T cells in BDC2.5 CD4+ T cell receptor transgenic Non-Obese Diabetic (NOD) mice (BDC2.5 + 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 BDC2.5 + NOD mice by generating Il-10-deficient BDC2.5 + NOD mice (BDC2.5 + Il-10 -/- NOD mice). Our results showed that BDC2.5 + Il-10 -/- NOD mice displayed robust and accelerated diabetes development. Il-10 deficiency in BDC2.5 + 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. In vitro studies showed that the gut microbiota from BDC2.5 + Il-10 -/- NOD mice can expand neutrophil populations. Moreover, in vivo studies demonstrated that the depletion of endogenous gut microbiota by antibiotic treatment decreased the proportion of neutrophils. Although Il-10 deficiency in BDC2.5 + 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 BDC2.5 + NOD mice, and suggests important crosstalk between gut microbiota and neutrophils in type 1 diabetes development.
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通过在胰腺淋巴结中发育调节的胰岛细胞抗原的发育表现来启动自身免疫性糖尿病。
DOI：
10.1084/jem.189.2.331
发表时间：
1999-01-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Höglund P;Mintern J;Waltzinger C;Heath W;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
11.1
作者：
Diana J;Lehuen A
通讯作者：
Lehuen A
影响因子：
30.5
作者：
Gonzalez, A;Andre-Schmutz, I;Benoist, C
通讯作者：
Benoist, C
影响因子：
24.5
作者：
Herfarth, HH;Mohanty, SP;Sartor, RB
通讯作者：
Sartor, RB
DOI：
10.1073/pnas.94.1.213
发表时间：
1997-01-07
影响因子：
11.1
作者：
Kurrer, MO;Pakala, SV;Katz, JD
通讯作者：
Katz, JD