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.

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.
2. GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK.
3. Université de Lyon, UR RTI2B, Lyon 69003, France.
4. Ecole Nationale Vétérinaire de Lyon, Lyon 69280, France.
5. Institut National de la Santé et de la Recherche Médicale, U601, Groupe de Recherche Cytokines et Récepteurs, Institut de Biologie, Nantes 44093, France.
6. Université de Nantes, Unité de Formation et de Recherche Médecine, IFR26, Institut de Biologie, Nantes 44093, France.
7. Hôpital de la Conception, Assistance Publique – Hôpitaux de Marseille, Marseille 13005, France.

Correspondence to: Eric Vivier^1,7 e-mail: vivier@ciml.univ-mrs.fr

Correspondence to: Thierry Walzer¹ e-mail: walzer@ciml.univ-mrs.fr

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