Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice.

Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice.
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DOI:
10.4049/jimmunol.1003523
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发表时间:
2011-07-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Wicker LS
Wicker LS
中科院分区:
其他
文献类型:
--
作者:
Rainbow DB;Moule C;Fraser HI;Clark J;Howlett SK;Burren O;Christensen M;Moody V;Steward CA;Mohammed JP;Fusakio ME;Masteller EL;Finger EB;Houchins JP;Naf D;Koentgen F;Ridgway WM;Todd JA;Bluestone JA;Peterson LB;Mattner J;Wicker LS

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我们之前提出,NOD 和 C57BL/6 (B6) 小鼠之间 CD101 基因的序列变异解释了 Idd10 区域(小鼠 3 号染色体上 <1 Mb 的区域)提供的对 1 型糖尿病 (T1D) 的保护。在这里,我们使用单倍型和与 CD101 敲除小鼠的发育相结合的新型 Idd10 同源品系的单倍型和表达分析,进一步支持了 Cd101 是 Idd10 的假设。 T1D 易感性与多个细胞亚群上基因型依赖性 CD101 表达相关,包括 FoxP3+ 调节性 CD4+ T 细胞、CD11c+ 树突状细胞和 Gr1+ 骨髓细胞。四种独立 Idd10 单倍型免疫细胞上 CD101 表达与 T1D 发展的相关性支持了 Cd101 与 Idd10 的同一性。由于 CD101 与 T 调节和抗原呈递细胞功能相关,因此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。
We have previously proposed that sequence variation of the CD101 gene between NOD and C57BL/6 (B6) mice accounts for the protection from type 1 diabetes (T1D) provided by the Idd10 region, a <1 Mb region on mouse chromosome 3. Here, 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. Since CD101 has been associated with T regulatory and antigen presentation cell functions, our results provide a further link between immune regulation and susceptibility to T1D.
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