Regulations of gene expression in medullary thymic epithelial cells required for preventing the onset of autoimmune diseases.
Regulations of gene expression in medullary thymic epithelial cells required for preventing the onset of autoimmune diseases.
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DOI：
10.3389/fimmu.2013.00249
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发表时间：
2013
影响因子：
7.3
通讯作者：
Akiyama N
中科院分区：
文献类型：
--
作者：
Akiyama T;Shinzawa M;Qin J;Akiyama N
消除胸腺中潜在的自身反应性 T 细胞对于预防自身免疫性疾病的发生至关重要。位于胸腺髓质的上皮细胞亚群[髓质胸腺上皮细胞 (mTEC)] 通过提供多种自身抗原来促进这一过程，这些抗原以组织特异性方式 (TSA) 表达。 mTECs 中某些 TSA 的表达受自身免疫调节蛋白 (AIRE) 的控制，其中功能失调的突变是自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良 (APECED) 的致病因素。除了消除自身反应性 T 细胞外，最近的研究还表明 mTEC 在 Foxp3 阳性调节性 T 细胞的发育中发挥作用，从而抑制自身免疫和外周组织中的过度免疫反应。 TNF 家族细胞因子、RANK 配体、CD40 配体和淋巴毒素被发现可促进表达 AIRE 和 TSA 的 mTEC 的分化。此外，NF-κB 的激活对于 mTEC 分化至关重要。在这篇小综述中，我们重点关注调节 AIRE 和 TSA 表达诱导的分子机制，并讨论这些机制对预防自身免疫性疾病发作的可能贡献。
Elimination of potential self-reactive T cells in the thymus is crucial for preventing the onset of autoimmune diseases. Epithelial cell subsets localized in thymic medulla [medullary thymic epithelial cells (mTECs)] contribute to this process by supplying a wide range of self-antigens that are otherwise expressed in a tissue-specific manner (TSAs). Expression of some TSAs in mTECs is controlled by the autoimmune regulator (AIRE) protein, of which dysfunctional mutations are the causative factor of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). In addition to the elimination of self-reactive T cells, recent studies indicated roles of mTECs in the development of Foxp3-positive regulatory T cells, which suppress autoimmunity and excess immune reactions in peripheral tissues. The TNF family cytokines, RANK ligand, CD40 ligand, and lymphotoxin were found to promote the differentiation of AIRE- and TSA-expressing mTECs. Furthermore, activation of NF-κB is essential for mTEC differentiation. In this mini-review, we focus on molecular mechanisms that regulate induction of AIRE and TSA expression and discuss possible contributions of these mechanisms to prevent the onset of autoimmune diseases.