Transcription Factor KLF10 Constrains IL-17-Committed Vγ4(+) γδ T Cells.

Transcription Factor KLF10 Constrains IL-17-Committed Vγ4(+) γδ T Cells.
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DOI:
10.3389/fimmu.2018.00196
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发表时间:
2018
影响因子:
7.3
通讯作者:
Yun CH
Yun CH
中科院分区:
医学2区
文献类型:
--
作者:
Kim G;Gu MJ;Kim SJ;Ko KH;Kye YC;Kim CG;Cho JH;Lee WK;Song KD;Chu H;Park YM;Han SH;Yun CH

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已知γδ T细胞是小鼠中先天性IL-17的重要来源,对宿主免疫应答提供关键贡献。γδ T细胞的发育和功能由多种转录因子(TF)的网络指导。在这里,我们研究了锌指转录因子Kruppel样因子10(KLF 10)在IL-17定向CD 27 − γδ T(γδ27−-17)细胞调节中的作用。我们发现,在KLF 10缺陷小鼠中,Vγ4+ γδ27−细胞的选择性增加具有更高的IL-17产生。令人惊讶的是,KLF 10缺陷型CD 127 hi Vγ4+ γδ27−-17细胞表达的CD 5水平高于野生型细胞,对细胞因子而不是T细胞受体刺激具有高反应性。在KLF 10缺陷的新生小鼠中,Vγ4+ γδ27−细胞的胸腺成熟增强。最后,一项混合骨髓嵌合体研究表明,内在KLF 10信号传导是限制Vγ4+ γδ27−-17细胞所必需的。总的来说,这些发现表明KLF 10调节Vγ4+ γδ27−细胞的胸腺发育及其稳态时的外周稳态。
γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27− γδ T (γδ27−-17) cells. We found selective augmentation of Vγ4+ γδ27− cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127hi Vγ4+ γδ27−-17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli. Thymic maturation of Vγ4+ γδ27− cells was enhanced in newborn mice deficient in KLF10. Finally, a mixed bone marrow chimera study indicates that intrinsic KLF10 signaling is requisite to limit Vγ4+ γδ27−-17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4+ γδ27− cells and their peripheral homeostasis at steady state.
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