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

Abstract

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 (γδ^27--17) cells. We found selective augmentation of Vγ4⁺ γδ^27- cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127^hi Vγ4⁺ γδ^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 Vγ4⁺ γδ^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 Vγ4⁺ γδ^27--17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4⁺ γδ^27- cells and their peripheral homeostasis at steady state.

Keywords: IL-17; Innate-like γδ-17; KLF10; homeostasis; γδ T cells.