CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes
CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes
复制标题
CD8+调节性T细胞在预防自身免疫介导的糖尿病中至关重要
DOI：
10.1038/s41467-020-15857-x
复制
发表时间：
2020-04-22
影响因子：
16.6
通讯作者：
Hisaeda, Hajime
中科院分区：
文献类型：
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作者：
Shimokawa, Chikako;Kato, Tamotsu;Hisaeda, Hajime
1型糖尿病（T1D）是一种自身免疫性疾病，其中产生胰岛素的胰腺β细胞被破坏。肠道蠕虫可引起无症状的慢性和免疫抑制感染，并抑制T1D啮齿动物模型中的疾病。然而，这种保护的基本监管机制尚不清楚。在这里，我们报告了CD8（+）调节性T细胞（Treg）细胞预防链脲佐菌素诱导的啮齿动物肠道线虫糖尿病的发作。来源于线虫的海藻糖影响肠道微生物群并增加瘤胃球菌属的丰度，导致CD8（+）Treg细胞的诱导。此外，海藻糖对链脲佐菌素诱导的糖尿病和NOD小鼠T1D模型均具有治疗作用。此外，与健康志愿者相比，T1D患者的CD8（+）Treg细胞更少，肠道瘤胃球菌的丰度与人体中CD8（+）Treg细胞的数量呈正相关。蠕虫感染与1型糖尿病啮齿动物模型中炎症病理学的减少相关。在这里，作者展示了患者数据，海藻糖（由H。polygyrus）可以改变小鼠的微生物组，诱导调节性CD8（+）T细胞，降低自身免疫性糖尿病的易感性。
Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing pancreatic beta -cells are destroyed. Intestinal helminths can cause asymptomatic chronic and immunosuppressive infections and suppress disease in rodent models of T1D. However, the underlying regulatory mechanisms for this protection are unclear. Here, we report that CD8(+) regulatory T (Treg) cells prevent the onset of streptozotocin -induced diabetes by a rodent intestinal nematode. Trehalose derived from nematodes affects the intestinal microbiota and increases the abundance of Ruminococcus spp., resulting in the induction of CD8(+) Treg cells. Furthermore, trehalose has therapeutic effects on both streptozotocin-induced diabetes and in the NOD mouse model of T1D. In addition, compared with healthy volunteers, patients with T1D have fewer CD8(+) Treg cells, and the abundance of intestinal Ruminococcus positively correlates with the number of CD8(+) Treg cells in humans. Helminth infections are associated with a reduction in inflammatory pathology in rodent models of type 1 diabetes. Here, the authors show patient data and that trehalose (produced by H. polygyrus) can alter the microbiome of mice, inducing regulatory CD8(+) T cells and reducing susceptibility to autoimmune diabetes.