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 (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.
Highlights
Studies on Kruppel-like factor 10 (KLF10), a transcription factor (TF) containing zinc finger DNA-binding domains, revealed its role in the induction of and balance between Foxp3+ regulatory T (Treg) cells and IL-17-producing T helper (Th17) cells [1,2,3]
KLF10 deficiency affected the expression level of CD5, a stable indicator of T-cell receptor (TCR) strength, on mature Vγ4+ γδ27−-17 cells within the neonatal thymus. These results suggest that the biology of Vγ4+ γδ27−-17 cells is dependent on transcriptional control by KLF10, which is differentially associated with TCR and cytokine signaling
Studies revealed that KLF10-deficient mice had defective Treg cell generation under inflammatory conditions, emphasizing the role of KLF10 as a TF in the balance between Treg and Th17 cell differentiation [1,2,3]
Summary
Studies on Kruppel-like factor 10 (KLF10), a transcription factor (TF) containing zinc finger DNA-binding domains, revealed its role in the induction of and balance between Foxp3+ regulatory T (Treg) cells and IL-17-producing T helper (Th17) cells [1,2,3]. The function of KLF10 in vivo is still unclear since the alteration of Treg cells in naïve KLF10-deficient mice is controversial [1,2,3] and the enrichment of Th17 cells in these mice has not been clearly reported. The functions of KLF10 in other T lymphocytes producing IL-17, such as γδ T cells, are largely unknown.
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