Kruppel-like factor 10 selectively constrains IL-17-committed 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. However, factors that control their development and homeostasis are poorly elucidated. Here I examine the role of the zinc finger transcription factor, Kruppel-like factor 10 (KLF10) in the development of IL-17-committed CD27- γδ T (γδ27--17) cells. I found a selective increase of Vγ4+ γδ27- cells with IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127hiVγ4+ γδ27--17 cells expressed CD5 higher than their wild-type counterparts, with hyper-responsiveness to cytokine and T-cell receptor stimuli. Maturation of Vγ4+ γδ27- cells was enhanced in newborn mice deficient in KLF10. Finally, mixed bone marrow chimera study indicated that intrinsic KLF10 signaling is mandatory 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.