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Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin

Nature Immunology volume 10, pages 75–82 (2009)Cite this article

Abstract

NKp46+CD3− natural killer lymphocytes isolated from blood, lymphoid organs, lung, liver and uterus can produce granule-dependent cytotoxicity and interferon-γ. Here we identify in dermis, gut lamina propria and cryptopatches distinct populations of NKp46+CD3− cells with a diminished capacity to degranulate and produce interferon-γ. In the gut, expression of the transcription factor RORγt, which is involved in the development of lymphoid tissue–inducer cells, defined a previously unknown subset of NKp46+CD3− lymphocytes. Unlike RORγt− lamina propria and dermis natural killer cells, gut RORγt+NKp46+ cells produced interleukin 22. Our data show that lymphoid tissue–inducer cells and natural killer cells shared unanticipated similarities and emphasize the heterogeneity of NKp46+CD3− cells in innate immunity, lymphoid organization and local tissue repair.

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Figure 1: Distribution of NKp46+CD3− cells in human and mouse gut and skin.
Figure 2: Phenotype of NKp46+CD3− cells in mouse gut and skin.
Figure 3: Effector functions of skin and gut NKp46+CD3− cells.
Figure 4: RORγt expression and analysis of NK1.1lo and NK1.1+ subsets of gut NKp46+CD3− cells.
Figure 5: Cytokine profiles of gut NKp46+CD3− cells.

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Acknowledgements

We thank the mouse functional genomics platform of Marseille-Nice Genopole for immunohistology; P. Grenot, M. Barad and A. Zouine from the Centre d'Immunologie de Marseille-Luminy flow cytometry core facility and M. Fallet from the Centre d'Immunologie de Marseille-Luminy microscopy facility for assistance; M. Betizeau for contributions to the initial phases of this work; M. Baratin, T. Walzer and S. Ugolini for discussions; and M. Ito (Central Institute for Experimental Animals) for Rag2−/−Il2rg−/− mice. Anti–human NKVSF1 was provided by A. Poggi (National Cancer Institute, Genoa, Italy), and anti-IL-22 (MH22B2) was provided by J.C. Renauld (Ludwig Institute for Cancer Research). E.V. and E.T. are joint senior authors. Supported by Ligue Nationale contre le Cancer ('Equipe labellisée La Ligue'), Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Ministère de l'Enseignement Supérieur et de la Recherche, Fondation pour la Recherche Medicale (C.L.), Region Provence Alpes Côte d′Azur–Institut National de la Santé et de la Recherche Médicale (A.R.), the Crohn's and Colitis Foundation of America (I.I.I.) and the Institut Universitaire de France (E.V.).

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Author notes

  1. Carmelo Luci, Ana Reynders and Ivaylo I Ivanov: These authors contributed equally to this work.

  2. vivier@ciml.univ-mrs.fr

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, Unité Mixte de Recherche 6102, case 906, Campus de Luminy, Marseille, 13288, France

    Carmelo Luci, Ana Reynders, Celine Cognet, Laurent Chiche, Lionel Chasson, Marc Dalod, Eric Vivier & Elena Tomasello

  2. The Kimmel Center for Biology and Medicine at the Skirball Institute and Howard Hughes Medical Institute, New York University School of Medicine, New York, 10016, New York, USA

    Ivaylo I Ivanov & Dan R Littman

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

    Celine Cognet, Laurent Chiche, Jean Hardwigsen & Eric Vivier

  4. Institut National de la Santé et de la Recherche Médicale, U899, Baylor Institute for Immunology Research, Dallas, 75204, Texas, USA

    Esperanza Anguiano, Jacques Banchereau & Damien Chaussabel

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Contributions

E.T. and E.V. designed the experiments and wrote the paper; E.T., C.L., A.R., I.I.I. and C.C. did and analyzed the experiments; Li.C. contributed to tissue section preparation and immunofluorescence staining; J.H. provided human samples; E.A., J.B. and D.C. did microarray hybridization and preliminary analysis; La.C. and M.D. contributed to microarray data analysis; and D.R.L. provided reagents crucial for the experiments and contributed to the design of the experiments and the interpretation of the data.

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Correspondence to Eric Vivier or Elena Tomasello.

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EV is a cofounder and shareholder of Innate-Pharma.

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Luci, C., Reynders, A., Ivanov, I. et al. Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin. Nat Immunol 10, 75–82 (2009). https://doi.org/10.1038/ni.1681

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