Nuclear factor (NF)-κB-inducing kinase (NIK) is known to be a critical regulator of multiple aspects of the immune response. Although the role of NIK in the development of medullary thymic epithelial cells (mTECs) has been well documented, the impact of NIK on the differentiation and function of cortical thymic epithelial cells (cTECs) remains ambiguous. To investigate the possible involvement of NIK in cTEC differentiation, we have compared the gene expression and function of cTECs from a NIK-mutant mouse, alymphoplasia (aly/aly) with those of cTECs from wild-type (WT) mice. Flow cytometric analyses revealed that expression levels of MHC class II, but not MHC class I or other TEC markers, were higher in aly/aly cells than in WT cells. Notably, the proportion of MHC class IIhi+ cTECs was elevated in aly/aly mice. We also demonstrated that expression of Ccl5 mRNA in the MHC class IIhi+ subset of aly/aly cTECs was decreased compared with that in WT cells, implying an abnormal pattern of gene expression in aly/aly cTECs. Analyses of bone marrow chimera using aly/aly or aly/+ mice as hosts suggested that Vβ usage and CD5 expression on WT T-cells were altered when they matured in aly/aly thymi. These results collectively indicate that NIK may be involved in controlling the function of cTEC in selecting a proper T-cell repertoire.

中文翻译：

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诱导NF-κB的激酶有助于皮层胸腺上皮细胞的正常发育：在塑造适当的T细胞库中可能发挥作用。

已知核因子（NF）-κB诱导激酶（NIK）是免疫反应多个方面的关键调节剂。尽管NIK在髓样胸腺上皮细胞（mTECs）发育中的作用已被充分证明，但NIK对皮质胸腺上皮细胞（cTECs）分化和功能的影响仍然不清楚。为了研究NIK在cTEC分化中的可能参与，我们比较了来自NIK突变型小鼠，无淋巴组织增生（aly / aly）的cTEC与野生型（WT）小鼠的cTEC的基因表达和功能。流式细胞仪分析显示，aly / aly细胞中II类MHC的表达水平高于WT细胞，但不高于I类MHC或其他TEC标记。值得注意的是，aly / aly小鼠的MHC IIhi + cTECs类比例增加。我们还证明，与WT细胞相比，aly / aly cTECs的MHC IIhi +亚类中Ccl5 mRNA的表达降低了，这暗示了aly / aly cTECs的基因表达异常。使用aly / aly或aly / +小鼠作为宿主的骨髓嵌合体分析表明，WT T细胞在aly / aly胸腺中成熟时，Vβ的用法和CD5表达改变。这些结果共同表明，NIK在选择合适的T细胞库中可能参与控制cTEC的功能。使用aly / aly或aly / +小鼠作为宿主的骨髓嵌合体分析表明，WT T细胞在aly / aly胸腺中成熟时，Vβ的用法和CD5表达改变。这些结果共同表明，NIK在选择合适的T细胞库中可能参与控制cTEC的功能。使用aly / aly或aly / +小鼠作为宿主的骨髓嵌合体分析表明，WT T细胞在aly / aly胸腺中成熟时，Vβ的用法和CD5表达改变。这些结果共同表明，NIK在选择合适的T细胞库中可能参与控制cTEC的功能。