转录调节因子 Aire 招募抑制性 ATF7ip-MBD1 复合物诱导免疫耐受。
The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.
机构信息
1] Diabetes Center, University of California San Francisco, San Francisco, California, USA. [2] Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.
Diabetes Center, University of California San Francisco, San Francisco, California, USA.
出版信息
Nat Immunol. 2014 Mar;15(3):258-65. doi: 10.1038/ni.2820. Epub 2014 Jan 26.
The maintenance of immunological tolerance requires the deletion of self-reactive T cells in the thymus. The expression of genes encoding tissue-specific antigens (TSAs) by thymic epithelial cells is critical for this process and depends on activity of the transcriptional regulator Aire; however, the molecular mechanisms Aire uses to target loci encoding TSAs are unknown. Here we identified two Aire-interacting proteins known to be involved in gene repression, ATF7ip and MBD1, that were required for Aire's targeting of loci encoding TSAs. Moreover, Mbd1(-/-) mice developed pathological autoimmunity and had a defect in Aire-dependent thymic expression of genes encoding TSAs, which underscores the importance of Aire's interaction with the ATF7ip-MBD1 protein complex in maintaining central tolerance.
免疫耐受的维持需要在胸腺中删除自身反应性 T 细胞。胸腺上皮细胞表达编码组织特异性抗原（TSAs）的基因对于这个过程至关重要，并且依赖于转录调节因子 Aire 的活性；然而，Aire 用于靶向编码 TSA 的基因座的分子机制尚不清楚。在这里，我们鉴定了两种已知参与基因抑制的与 Aire 相互作用的蛋白质，即 ATF7ip 和 MBD1，它们是 Aire 靶向编码 TSA 的基因座所必需的。此外，Mbd1(-/-) 小鼠发生病理性自身免疫，并且在 Aire 依赖性胸腺表达编码 TSA 的基因中存在缺陷，这突出了 Aire 与 ATF7ip-MBD1 蛋白复合物相互作用在维持中枢耐受中的重要性。
Zotero 插件