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Natural killer cell trafficking in vivo requires a dedicated sphingosine 1-phosphate receptor

Nature Immunology volume 8, pages 1337–1344 (2007)Cite this article

Abstract

Consistent with their function in immune surveillance, natural killer (NK) cells are distributed throughout lymphoid and nonlymphoid tissues. However, the mechanisms governing the steady-state trafficking of NK cells remain unknown. The lysophospholipid sphingosine 1-phosphate (S1P), by binding to its receptor S1P1, regulates the recirculation of T and B lymphocytes. In contrast, S1P5 is detected in the brain and regulates oligodendrocyte migration and survival in vitro. Here we show that S1P5 was also expressed in NK cells in mice and humans and that S1P5-deficient mice had aberrant NK cell homing during steady-state conditions. In addition, we found that S1P5 was required for the mobilization of NK cells to inflamed organs. Our data emphasize distinct mechanisms regulating the circulation of various lymphocyte subsets and raise the possibility that NK cell trafficking may be manipulated by therapies specifically targeting S1P5.

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Figure 1: Expression of genes encoding S1P receptors in mouse lymphocytes.
Figure 2: Steady-state tissue distribution of NK cells wild-type and S1P5-deficient mice.
Figure 3: Tissue distribution of NK cells in wild-type and S1P5-deficient mice treated with IL-15.
Figure 4: NK cell–intrinsic function for S1P5 in NK cell tissue distribution.
Figure 5: Effect of S1P5 deficiency on the tissue distribution of NK cell subsets.
Figure 6: Defective in vivo and in vitro migration of S1P5-deficient NK cells.
Figure 7: Pharmacological modulation of NK cell trafficking.

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Acknowledgements

We thank L. Chasson and the mouse functional genomics platform of the Marseille-Nice Genopole for immunohistochemistry; B. Malissen, J. Ewbank, C. Luci and S. Ugolini for discussions; and N. Fuseri (Innate-Pharma, Marseille) for mouse housing. FTY720 was provided by V. Brinkmann (Novartis). Supported by European Union Sixth Framework Programme, LSHB-CT-2004-503319-Allostem, Ligue Nationale contre le Cancer ('Equipe labellisée La Ligue'), Agence Nationale de la Recherche ('Réseau Innovation Biotechnologies' and 'Microbiologie Immunologie–Maladies Emergentes'”), Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique and Ministère de l'Enseignement Supérieur et de la Recherche.

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Authors and Affiliations

  1. Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Institut National de la Santé et de la Recherche Médicale, U631, and Centre National de la Recherche Scientifique, UMR6102, Case 906, Campus de Luminy, Marseille, 13288, France

    Thierry Walzer, Laura Chiossone, Julie Chaix, Myriam Baratin, Elena Tomasello & Eric Vivier

  2. GlaxoSmithKline, New Frontiers Science Park, Harlow, CM19 5AW, Essex, UK

    Andrew Calver

  3. Université de Lyon, UR RTI2B, Lyon, 69003, France

    Claude Carozzo

  4. Ecole Nationale Vétérinaire de Lyon, Lyon, 69280, France

    Claude Carozzo

  5. Institut National de la Santé et de la Recherche Médicale, U601, Groupe de Recherche Cytokines et Récepteurs, Institut de Biologie, Nantes, 44093, France

    Laure Garrigue-Antar & Yannick Jacques

  6. Université de Nantes, Unité de Formation et de Recherche Médecine, IFR26, Institut de Biologie, Nantes, 44093, France

    Laure Garrigue-Antar & Yannick Jacques

  7. Hôpital de la Conception, Assistance Publique – Hôpitaux de Marseille, Marseille, 13005, France

    Eric Vivier

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Contributions

T.W. and E.V. designed the experiments and wrote the paper; T.W. did experiments for Figures 2, 3, 4, 5, 6, 7; L.C. did experiments for Figures 2 and 6 and Supplementary Figure 3; J.C. did experiments for Figures 1 and 5; A.C. provided S1P5-deficient mice, Y.J. and L.G.-A. provided RLI; E.T. did experiments for Supplementary Figure 2; M.B. contributed to analysis of the results; and C.C. did experiments not shown and contributed to analysis of the results.

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Correspondence to Thierry Walzer or Eric Vivier.

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Competing interests

A.C. is an employee of Glaxo-SmithKline; E.V. is a c-founder and shareholder of Innate-Pharma.

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Walzer, T., Chiossone, L., Chaix, J. et al. Natural killer cell trafficking in vivo requires a dedicated sphingosine 1-phosphate receptor. Nat Immunol 8, 1337–1344 (2007). https://doi.org/10.1038/ni1523

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