Kruppel-like factor 2 controls T cell trafficking by activating L-selectin (CD62L) and sphingosine-1-phosphate receptor 1 transcription.
Krüppel-like factor 2 (KLF2) is a member of zinc-finger transcription factors. Based on its expression in naive and memory T cells and the activated phenotype of few T cells in mice lacking KLF2 in the lymphoid lineage, KLF2 is postulated to regulate T cell homeostasis by promoting cell quiescence. In this study, we show that in reporter gene assays KLF2 directly activates the promoters of both CD62L and sphingosine-1-phosphate receptor 1 (S1P1), whose expression is critical for T cell egress from the thymus and homing to the lymph nodes. Correspondingly, exogenous KLF2 expression in primary T cells significantly up-regulates both CD62L and S1P1. Following adoptive transfer, KLF2-transduced T cells are much more efficient in homing to lymphoid organs than nontransduced T cells. These findings suggest that KLF2 regulates T cell homeostasis at least partly by controlling CD62L and S1P1 expression, and therefore T cell egress from the thymus and circulation in the periphery.
Bai
Ailin
A
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, 40 Ames Street, Cambridge, MA 02139, USA.
Hu
Hui
H
Yeung
Mandy
M
Chen
Jianzhu
J
D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019041:L-Selectin / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D049349:Receptors, Lysosphingolipid / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D049349:Receptors, Lysosphingolipid; D019041:L-Selectin; D015847:Interleukin-4