Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.
Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
Diabetes. 2020 Apr;69(4):661-669. doi: 10.2337/db19-0751. Epub 2020 Jan 2.
Autoimmunity against pancreatic β-cell autoantigens is a characteristic of childhood type 1 diabetes (T1D). Autoimmunity usually appears in genetically susceptible children with the development of autoantibodies against (pro)insulin in early childhood. The offspring of mothers with T1D are protected from this process. The aim of this study was to determine whether the protection conferred by maternal T1D is associated with improved neonatal tolerance against (pro)insulin. Consistent with improved neonatal tolerance, the offspring of mothers with T1D had reduced cord blood CD4 T-cell responses to proinsulin and insulin, a reduction in the inflammatory profile of their proinsulin-responsive CD4 T cells, and improved regulation of CD4 T cell responses to proinsulin at 9 months of age, as compared with offspring with a father or sibling with T1D. Maternal T1D was also associated with a modest reduction in CpG methylation of the gene in cord blood mononuclear cells from offspring with a susceptible genotype. Our findings support the concept that a maternal T1D environment improves neonatal immune tolerance against the autoantigen (pro)insulin.
自身免疫对胰腺β细胞自身抗原的自身免疫是儿童 1 型糖尿病（T1D）的特征。自身免疫通常出现在具有（前）胰岛素自身抗体的遗传易感儿童中，这些自身抗体在幼儿期出现。患有 T1D 的母亲的后代可免受此过程的影响。本研究的目的是确定母体 T1D 赋予的保护是否与对（前）胰岛素的新生儿耐受性改善有关。与新生儿耐受性改善一致，与患有 T1D 的父亲或兄弟姐妹的后代相比，患有 T1D 的母亲的后代对前胰岛素和胰岛素的脐带血 CD4 T 细胞反应减少，对前胰岛素反应的 CD4 T 细胞的炎症特征减少，并且在 9 个月时对前胰岛素的 CD4 T 细胞反应的调节得到改善。母体 T1D 还与易感基因型的后代脐带血单核细胞中 基因的 CpG 甲基化适度减少有关。我们的发现支持这样一种概念，即母体 T1D 环境可改善新生儿对自身抗原（前）胰岛素的免疫耐受性。
