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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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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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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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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DOI: https://doi.org/10.1038/ni.1681
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