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Transcription factor KLF2 regulates the migration of naive T cells by restricting chemokine receptor expression patterns

Nature Immunology volume 9, pages 292–300 (2008)Cite this article

Abstract

The migration patterns of naive and activated T cells are associated with the expression of distinct sets of chemokine receptors, but the molecular basis for this regulation is unknown. Here we identify Krupple-like factor 2 (KLF2) as a key transcriptional factor needed to prevent naive T cells from expressing inflammatory chemokine receptors and acquiring the migration patterns of activated T cells. Lineage-specific deletion of KLF2 resulted in fewer naive T cells in the blood and secondary lymphoid organs, whereas it expanded naive T cell numbers in nonlymphoid tissues; these effects were associated with altered expression of inflammatory chemokine receptors on naive T cells. KLF2 repressed the expression of several chemokine receptors, including CCR3 and CCR5. We thus conclude that KLF2 maintains proper T cell migration patterns by linking T cell movement and transcriptional regulation of chemokine receptor expression patterns.

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Figure 1: Klf2−/−Vav-Cre+ mice have more mature thymocytes but many fewer T cells in the peripheral blood and lymphoid organs.
Figure 2: KLF2-deficient thymocytes and T cells do not undergo spontaneous apoptosis.
Figure 3: CD4+ T cell migration in response to S1P and inhibition of migration by FTY720 indicates the presence of peripheral KLF2-deficient T cells in Klf2fl/flVav-Cre− mice.
Figure 4: KLF2-deficient T cells trapped in lymph nodes by FTY720 treatment have a naive phenotype.
Figure 5: KLF2-deficient T cells home to nonlymphoid peripheral tissues.
Figure 6: Expression and function of inflammatory chemokine receptors by naive KLF2-deficient T cells.
Figure 7: Altered homing by KLF2-deficient T cells in vivo requires Gi protein–coupled chemokine receptor signaling.

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Acknowledgements

We thank J. Cyster and M. Zachariah for assistance with anti-S1P1 staining and for comments on the manuscript; T. Graf (Albert Einstein College of Medicine) for the use of Vav-Cre–transgenic mice; and G. Koretzky, J. Maltzman and B. Kleaveland for insights. The plasmid pcDNA-HA-KLF2 was a gift from laboratory of L.H. Glimcher (Harvard School of Public Health).

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  1. Eric Sebzda

    Present address: Present address: Department of Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee 37232, USA.,

Authors and Affiliations

  1. Department of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Eric Sebzda, Zhiying Zou, John S Lee, Tao Wang & Mark L Kahn

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E.S. designed and did experiments and wrote the manuscript; Z.Z., J.S.L. and T.W. designed and did experiments; and M.L.K. designed experiments and wrote the manuscript.

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Correspondence to Eric Sebzda or Mark L Kahn.

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Sebzda, E., Zou, Z., Lee, J. et al. Transcription factor KLF2 regulates the migration of naive T cells by restricting chemokine receptor expression patterns. Nat Immunol 9, 292–300 (2008). https://doi.org/10.1038/ni1565

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