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

CM Carlson, BT Endrizzi, J Wu, X Ding, MA Weinreich… - Nature, 2006 - nature.com
CM Carlson, BT Endrizzi, J Wu, X Ding, MA Weinreich, ER Walsh, MA Wani, JB Lingrel…
Nature, 2006nature.com
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 …
Abstract
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.
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