Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells
Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells
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Runt 相关转录因子 3 参与 ThPok 缺陷的不变自然杀伤 T 细胞表型和功能的改变
DOI：
10.1038/cmi.2014.3
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发表时间：
2014-05-01
影响因子：
24.1
通讯作者：
Wang, Jianli
中科院分区：
文献类型：
--
作者：
Liu, Xia;Yin, Shengxia;Wang, Jianli
CD4 谱系转录因子 ThPok 和 CD8 谱系转录因子、runt 相关转录因子 3 (Runx3) 在 T 细胞发育过程中的相互作用已被广泛记录。然而，人们对这些转录因子在不变自然杀伤 T (iNKT) 细胞发育中的作用知之甚少。 CD1d 限制性 iNKT 细胞属于 CD4+ CD8− 和 CD4− CD8− 亚系，这些亚系通过快速有效地释放 T 辅助细胞 (Th) 1 和 Th2 细胞因子来响应抗原刺激。然而，之前的报告已经证明 ThPok 缺陷小鼠体内存在新的 CD8+ NKT 细胞群。在当前的研究中，我们试图确定在 ThPok 缺失的情况下 Runx3 是否参与 CD8 的重新表达和 iNKT 细胞的功能。我们使用缺乏 Runx3、ThPok 或两者的小鼠，并验证 Runx3 对 ThPok 敲除小鼠中 CD8+ iNKT 细胞的出现负有部分责任。此外，Runx3 参与了 α-半乳糖神经酰胺诱导的急性肝炎模型中 iNKT 细胞介导的免疫反应。这些结果表明 Runx3 对于 ThPok 缺陷的 iNKT 细胞中观察到的表型和功能变化至关重要。
The interplay between the CD4-lineage transcription factor ThPok and the CD8-lineage transcription factor, runt-related transcription factor 3 (Runx3), in T-cell development has been extensively documented. However, little is known about the roles of these transcription factors in invariant natural killer T (iNKT) cell development. CD1d-restricted iNKT cells are committed to the CD4+ CD8− and CD4− CD8− sublineages, which respond to antigen stimulation with rapid and potent release of T helper (Th) 1 and Th2 cytokines. However, previous reports have demonstrated a new population of CD8+ NKT cells in ThPok-deficient mice. In the current study, we sought to determine whether Runx3 was involved in the re-expression of CD8 and function of iNKT cells in the absence of ThPok. We used mice lacking Runx3, ThPok or both and verified that Runx3 was partially responsible for the appearance of CD8+ iNKT cells in ThPok knockout mice. Additionally, Runx3 participated in the immune response mediated by iNKT cells in a model of α-galactosylceramide-induced acute hepatitis. These results indicate that Runx3 is crucial for the phenotypic and functional changes observed in ThPok-deficient iNKT cells.