Kruppel-like factor 2 regulates thymocyte and T-cell migration

Mammalian Kruppel-like transcription factors are implicated in regulating terminal differentiation of several tissue types(1-3). Deficiency in Kruppel-like factor (KLF) 2 ( also known as LKLF) leads to a massive loss of the peripheral T-cell pool(4), suggesting KLF2 regulates T-cell quiescence and survival(4-7). Here we show, however, that KLF2 is essential for T-cell trafficking. KLF2-deficient (Klf2(-/-)) thymocytes show impaired expression of several receptors required for thymocyte emigration and peripheral trafficking, including the sphingosine-1-phosphate (S1P) receptor S1P(1), CD62L and beta(7) integrin. Furthermore, KLF2 both binds and transactivates the promoter for S1P(1) - a receptor that is critical for thymocyte egress and recirculation through peripheral lymphoid organs. Our findings suggest that KLF2 serves to license mature T cells for trafficking from the thymus and recirculation through secondary lymphoid tissues.