Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom.
J Immunol. 2011 Jul 1;187(1):325-36. doi: 10.4049/jimmunol.1003523. Epub 2011 May 25.
We have previously proposed that sequence variation of the CD101 gene between NOD and C57BL/6 mice accounts for the protection from type 1 diabetes (T1D) provided by the insulin-dependent diabetes susceptibility region 10 (Idd10), a <1 Mb region on mouse chromosome 3. In this study, we provide further support for the hypothesis that Cd101 is Idd10 using haplotype and expression analyses of novel Idd10 congenic strains coupled to the development of a CD101 knockout mouse. Susceptibility to T1D was correlated with genotype-dependent CD101 expression on multiple cell subsets, including Foxp3(+) regulatory CD4(+) T cells, CD11c(+) dendritic cells, and Gr1(+) myeloid cells. The correlation of CD101 expression on immune cells from four independent Idd10 haplotypes with the development of T1D supports the identity of Cd101 as Idd10. Because CD101 has been associated with regulatory T and Ag presentation cell functions, our results provide a further link between immune regulation and susceptibility to T1D.
我们之前提出，NOD 和 C57BL/6 小鼠之间 CD101 基因的序列变异解释了胰岛素依赖型糖尿病易感区域 10（Idd10）提供的 1 Mb 左右的小鼠 3 号染色体上的 1 型糖尿病（T1D）保护作用。在这项研究中，我们通过对新型 Idd10 同系交配品系的单倍型和表达分析，为 Cd101 是 Idd10 的假设提供了进一步的支持，并开发了 CD101 敲除小鼠。T1D 的易感性与多种细胞亚群（包括 Foxp3(+)调节性 CD4(+)T 细胞、CD11c(+)树突状细胞和 Gr1(+)髓样细胞）上依赖于基因型的 CD101 表达相关。从四个独立的 Idd10 单倍型的免疫细胞上的 CD101 表达与 T1D 的发展之间的相关性支持 Cd101 是 Idd10 的身份。因为 CD101 与调节性 T 细胞和抗原呈递细胞功能有关，所以我们的结果提供了免疫调节与 T1D 易感性之间的进一步联系。
