Cell-intrinsic role for NF-kappa B-inducing kinase in peripheral maintenance but not thymic development of Foxp3+ regulatory T cells in mice.
Cell-intrinsic role for NF-kappa B-inducing kinase in peripheral maintenance but not thymic development of Foxp3+ regulatory T cells in mice.
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DOI：
10.1371/journal.pone.0076216
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Murray SE
中科院分区：
文献类型：
--
作者：
Murray SE
NF-κB诱导激酶（NIK，MAP 3 K14）是非经典NF-κB活化的关键信号分子，NIK缺陷小鼠有助于阐明该途径的免疫学作用。NIK的整体消融阻止淋巴结发育，损害胸腺基质发育，并显著减少B细胞。尽管胸腺选择改变，但NIK缺陷小鼠的T细胞数量接近正常。例外的是CD 4+调节性T细胞（TCRs），其在胸腺和外周中减少。已知胸腺基质中的缺陷有助于受损的Treg生成，但NIK是否也在Treg中发挥细胞内在作用尚不清楚。在这里，我们将完整小鼠与单一和混合的BM嵌合小鼠进行比较，以评估NIK在Treg生成和维持中的内在作用。我们发现，虽然NIK在基质细胞中的表达足以满足正常胸腺Treg发育，但NIK是维持外周Treg所必需的细胞固有的。此外，我们意外地发现了NIK在记忆表型常规T细胞中的细胞内在作用，其在完整小鼠中被掩蔽，但在BM嵌合体中被揭示。这些结果证明了NIK在外周调节和记忆表型T细胞稳态中的新作用。
NF-κB inducing kinase (NIK, MAP3K14) is a key signaling molecule in non-canonical NF-κB activation, and NIK deficient mice have been instrumental in deciphering the immunologic role of this pathway. Global ablation of NIK prevents lymph node development, impairs thymic stromal development, and drastically reduces B cells. Despite altered thymic selection, T cell numbers are near normal in NIK deficient mice. The exception is CD4+ regulatory T cells (Tregs), which are reduced in the thymus and periphery. Defects in thymic stroma are known to contribute to impaired Treg generation, but whether NIK also plays a cell intrinsic role in Tregs is unknown. Here, we compared intact mice with single and mixed BM chimeric mice to assess the intrinsic role of NIK in Treg generation and maintenance. We found that while NIK expression in stromal cells suffices for normal thymic Treg development, NIK is required cell-intrinsically to maintain peripheral Tregs. In addition, we unexpectedly discovered a cell-intrinsic role for NIK in memory phenotype conventional T cells that is masked in intact mice, but revealed in BM chimeras. These results demonstrate a novel role for NIK in peripheral regulatory and memory phenotype T cell homeostasis.
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影响因子：
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作者：
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影响因子：
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DOI：
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