Data_Sheet_6.PDF

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.γδ T细胞（γδ T cells）作为小鼠体内天然性白细胞介素17（IL-17）的重要来源，在宿主免疫应答中发挥关键作用。γδ T细胞的发育与功能受多样化转录因子（transcription factors, TFs）构成的调控网络所支配。本研究探讨了锌指类转录因子Krüppel样因子10（KLF10）在白细胞介素17定向分化的CD27阴性γδ T（γδ27−-17）细胞调控中的作用。我们发现，在KLF10缺陷型小鼠中，IL-17分泌水平更高的Vγ4阳性γδ27−细胞出现选择性扩增。令人意外的是，KLF10缺陷的CD127高表达Vγ4阳性γδ27−-17细胞，其CD5表达水平较野生型对照更高，且对细胞因子刺激呈现超敏反应，但对T细胞受体（T-cell receptor, TCR）刺激无此响应。在KLF10缺陷的新生小鼠体内，Vγ4阳性γδ27−细胞的胸腺成熟过程得到增强。最后，混合骨髓嵌合体研究表明，内源性KLF10信号通路是限制Vγ4阳性γδ27−-17细胞的必要条件。综上，这些发现证实KLF10可调控Vγ4阳性γδ27−细胞的胸腺发育，并在稳态下维持其外周稳态。