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Krüppel-Like Factor 2 Controls T Cell Trafficking by Activating L-Selectin (CD62L) and Sphingosine-1-Phosphate Receptor 1 Transcription¹

Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported partly by National Institutes of Health Grants AI50631 and AI40146 and Koch Research Fund (to J.C.), and a core grant to the Massachusetts Institute of Technology Center for Cancer Research (CA140451). A.B. was partly supported by the Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship and postdoctoral fellowships from the Sorono Foundation and National Institutes of Health.

² Address correspondence and reprint requests to Dr. Jianzhu Chen, Center for Cancer Research and Department of Biology, 40 Ames Street, Cambridge, MA 02139. E-mail address: jchen{at}mit.edu

³ Abbreviations used in this paper: KLF2, Krüppel-like factor 2; _c, common -chain; HA, hemagglutinin; S1P, sphingosine-1-phosphate; S1P1, S1P receptor 1; SDF-1, stromal cell derived factor-1; SP, single positive; T_CM, central memory T; T_EM, effector memory T.

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