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Abstract

<p>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 CD127^hi 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.</p