TNF receptor family signaling in the development and functions of medullary thymic epithelial cells.
TNF receptor family signaling in the development and functions of medullary thymic epithelial cells.
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DOI：
10.3389/fimmu.2012.00278
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发表时间：
2012
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;Akiyama N
胸腺上皮细胞（TEC）提供胸腺中T细胞发育所需的微环境。胸腺髓质上皮细胞（mTECs）的一个独特性质是它们表达广泛的组织限制性自身抗原，其由核蛋白AIRE严格调节，这有助于选择自身耐受性T细胞库，从而抑制自身免疫性疾病的发作。肿瘤坏死因子受体家族（TNF receptor family，TNFRF）的NF-κB受体激活因子（protein receptor activator of NF-κB，RANK）、CD 40和光毒素β受体（apoptoxin β receptor，LtβR）参与调节mTECs的发育和功能。这些受体与其特异性配体的结合导致转录因子NF-κB家族的活化。两种NF-κB激活途径（经典和非经典途径）促进这些受体诱导的成熟mTEC的发育。因此，经典途径的信号转导子TNF受体相关因子（TRAF 6）和非经典途径的信号转导子NF-κB诱导激酶（NIK）对成熟mTECs的发育至关重要。本文综述了目前对TNF受体家族的信号传导如何控制mTEC的发育和功能的认识。
Thymic epithelial cells (TECs) provide the microenvironment required for the development of T cells in the thymus. A unique property of medullary thymic epithelial cells (mTECs) is their expression of a wide range of tissue-restricted self-antigens, critically regulated by the nuclear protein AIRE, which contributes to the selection of the self-tolerant T cell repertoire, thereby suppressing the onset of autoimmune diseases. The TNF receptor family (TNFRF) protein receptor activator of NF-κB (RANK), CD40 and lymphotoxin β receptor (LtβR) regulate the development and functions of mTECs. The engagement of these receptors with their specific ligands results in the activation of the NF-κB family of transcription factors. Two NF-κB activation pathways, the classical and non-classical pathways, promote the development of mature mTECs induced by these receptors. Consistently, TNF receptor-associated factor (TRAF6), the signal transducer of the classical pathway, and NF-κB inducing kinase (NIK), the signal transducer of the non-classical pathway, are essential for the development of mature mTECs. This review summarizes the current understanding of how the signaling by the TNF receptor family controls the development and functions of mTEC.