Transcription Factor KLF10 constrains IL-17-committed Vγ4⁺ γδT cells

초록

gamma delta 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 ye) T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TF, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27-gamma delta T (gamma delta 27(-)-17) cells. We found selective augmentation of V gamma 4+ gamma delta 27(-)cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127(hi) V gamma 4(+)gamma delta 27(-)-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 V gamma 4(+) gamma delta 27- 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 V gamma 4+ y delta 27(-)-17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of V gamma 4(+) gamma delta 27(-) cells and their peripheral homeostasis at steady state.

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