NF-kappa B-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner.
NF-kappa B-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner.
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发表时间：
2004
影响因子：
4.4
通讯作者：
Fumiko Kajiura;Shijie Sun;T. Nomura;K. Izumi;T. Ueno;Y. Bando;N. Kuroda;Hongwei Han;Yi Li
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文献类型：
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作者：
Fumiko Kajiura;Shijie Sun;T. Nomura;K. Izumi;T. Ueno;Y. Bando;N. Kuroda;Hongwei Han;Yi Li
胸腺细胞和胸腺基质之间的物理接触是T细胞成熟所必需的，并塑造了外周的T细胞库。控制这些过程的基质元素仍然难以捉摸。我们使用带有突变的核因子-kappaB诱导激酶(NIK)的小鼠品系来研究自我耐受性崩溃的机制。该突变株表现为自身免疫和胸腺结构紊乱，间质中Rel蛋白表达异常。在Nik突变小鼠中，控制自身反应性T细胞的免疫调节性T细胞的产生受到损害。从Nik突变小鼠身上看到的自身免疫性疾病是通过移植Nik突变小鼠的胚胎胸腺在裸鼠身上复制的，这是通过提供外源免疫调节T细胞来挽救的。缺乏NIK的胸腺基质免疫调节性T细胞的产生受损与外周组织限制性AGS的表达改变有关，提示NIK在胸腺微环境中在建立中枢耐受中起着重要作用。
Physical contact between thymocytes and the thymic stroma is essential for T cell maturation and shapes the T cell repertoire in the periphery. Stromal elements that control these processes still remain elusive. We used a mouse strain with mutant NF-kappaB-inducing kinase (NIK) to examine the mechanisms underlying the breakdown of self-tolerance. This NIK-mutant strain manifests autoimmunity and disorganized thymic structure with abnormal expression of Rel proteins in the stroma. Production of immunoregulatory T cells that control autoreactive T cells was impaired in NIK-mutant mice. The autoimmune disease seen in NIK-mutant mice was reproduced in athymic nude mice by grafting embryonic thymus from NIK-mutant mice, and this was rescued by supply of exogenous immunoregulatory T cells. Impaired production of immunoregulatory T cells by thymic stroma without normal NIK was associated with altered expression of peripheral tissue-restricted Ags, suggesting an essential role of NIK in the thymic microenvironment in the establishment of central tolerance.