Mammalian Kruppel-like transcription factors are implicated in regulating terminal differentiation of several tissue types. Deficiency in Kruppel-like factor (KLF) 2 (also known as LKLF) leads to a massive loss of the peripheral T-cell pool, suggesting KLF2 regulates T-cell quiescence and survival. 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 S1P1, CD62L and Β7 integrin. Furthermore, KLF2 both binds and transactivates the promoter for S1P1 - 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.
|Original language||English (US)|
|Number of pages||4|
|State||Published - Jul 20 2006|
Bibliographical noteFunding Information:
Acknowledgements We thank J. Cyster for generous provision of CCL19–Fc fusion protein, Y. Li for developing S1P1 RT–PCR assays, M. Jenkins and M. Mescher for critical input on the manuscript, and members of the ‘Jamequist’ laboratory for helpful discussions. This work was supported by the NIH (an immunology pre-doctoral training grant to B.T.E., a grant to K.A.H., and a grant to S.C.J.), the American Cancer Society (a grant to S.C.J.), and the Cancer Research Institute (post-doctoral fellowship to C.M.C.).