Role of Krüppel-like factor 4 (Klf4) in regulation of T cell number and TH-17 differentiation (139.12)

Abstract

Abstract Krüppel-like factor 4 (Klf4), a zinc finger-containing transcription factor of the Krüppel-like factor family, plays critical role in cell differentiation, growth, and cycle. We report here a role of Klf4 in T cell development and differentiation. The expression of Klf4 was high in thymocytes and resting mature T cells, and was down-regulated in activated mature T cells. In the absence of Klf4, modest but significant reductions of T cell numbers in thymus (~27%) and in spleen (~25%), and a similar degree reduction of spleen CD4 T cells and a less degree loss of spleen CD8 T cells were found in Klf4 deficient mice. Gene expression analysis revealed an alteration of genes involved in cell cycling and proliferation in the absence of Klf4 in thymocytes, implying their role in control of T cell number. Furthermore, we found that significant reduction of IL-17 expressing CD4 T cells (TH-17) during in vitro differentiation in mice absence of Klf4 compared to the wild-type mice. We then demonstrated that Klf4 directly binds the promoter of IL17a but not to the promoter of ROR-γt gene, suggesting that Klf4 directly regulates Il17a in TH-17 differentiation. Together, these findings demonstrate that Klf4 regulates T cell development and TH-17 differentiation.