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. 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 beta7 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.
Carlson
Corey M
CM
Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Endrizzi
Bart T
BT
Wu
Jinghai
J
Ding
Xiaojie
X
Weinreich
Michael A
MA
Walsh
Elizabeth R
ER
Wani
Maqsood A
MA
Lingrel
Jerry B
JB
Hogquist
Kristin A
KA
Jameson
Stephen C
SC
D019264:Adoptive Transfer; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D002678:Chimera / Q000378:metabolism; D005333:Fetus; D006801:Humans; D019169:Jurkat Cells; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000196:embryology; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D049349:Receptors, Lysosphingolipid / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology*; D015533:Transcriptional Activation
C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D049349:Receptors, Lysosphingolipid