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

Nature volume 442, pages 299–302 (2006)Cite this article

Abstract

Mammalian Kruppel-like transcription factors are implicated in regulating terminal differentiation of several tissue types1,2,3. Deficiency in Kruppel-like factor (KLF) 2 (also known as LKLF) leads to a massive loss of the peripheral T-cell pool4, suggesting KLF2 regulates T-cell quiescence and survival4,5,6,7. 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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Figure 1: Klf2 -/- T cells develop but do not populate the periphery in fetal liver chimaeras.
Figure 2: Klf2 -/- T cells survive but show deregulated trafficking following adoptive transfer.
Figure 3: KLF2 is required for thymocyte expression of critical trafficking molecules.
Figure 4: KLF2 transactivates the S1P 1 promoter.

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Acknowledgements

We thank J. Cyster for generous provision of CCL19–Fc fusion protein, Y. Li for developing S1P1 RT–PCR assays, M. Jenkins and M. Mescher for critical input on the manuscript, and members of the ‘Jamequist’ laboratory for helpful discussions. This work was supported by the NIH (an immunology pre-doctoral training grant to B.T.E., a grant to K.A.H., and a grant to S.C.J.), the American Cancer Society (a grant to S.C.J.), and the Cancer Research Institute (post-doctoral fellowship to C.M.C.).

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  1. Corey M. Carlson and Bart T. Endrizzi: *These authors contributed equally to this work

Authors and Affiliations

  1. Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota, 55455, USA

    Corey M. Carlson, Bart T. Endrizzi, Xiaojie Ding, Michael A. Weinreich, Elizabeth R. Walsh, Kristin A. Hogquist & Stephen C. Jameson

  2. Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, Ohio, 45267, USA

    Jinghai Wu, Maqsood A. Wani & Jerry B. Lingrel

Authors
  1. Corey M. Carlson
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Correspondence to Kristin A. Hogquist or Stephen C. Jameson.

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Supplementary information

Supplementary Notes

This file contains Supplementary Methods with eight references, details of grant support and Supplementary Figures S1–S4 with legends. Supplementary Figure S1 details the normal in vitro survival of KLF2-/- mature thymocytes. Supplementary Figure S2 shows aberrant trafficking and phenotype of KLF2-/- SP thymocytes after adoptive transfer. Supplementary Figure S3 details real-time PCR analysis of gene expression in KLF2-/- and KLF2+/- DP and CD4 SP thymocytes. Supplementary Figure S4 shows the sequence of human and mouse S1P1 promoters, showing the CACCC sequence and the location of primers used for the CHiP assay. (PDF 453 kb)

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Carlson, C., Endrizzi, B., Wu, J. et al. Kruppel-like factor 2 regulates thymocyte and T-cell migration. Nature 442, 299–302 (2006). https://doi.org/10.1038/nature04882

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