Identity, regulation and in vivo function of gut NKp46(+)RORγt(+) and NKp46(+)RORγt(-) lymphoid cells.
2011
Reynders, Ana | Yessaad, Nadia | Vu Manh, Thien-Phong | Dalod, Marc | Fenis, Aurore | Aubry, Camille | Nikitas, Georgios | Escalière, Bertrand | Renauld, Jean Christophe | Dussurget, Olivier | Cossart, Pascale | Lecuit, Marc | Vivier, Eric | Tomasello, Elena | Centre d'Immunologie de Marseille - Luminy (CIML) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Interactions Bactéries-Cellules (UIBC) ; Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Microorganismes et Barrières de l'Hôte (Equipe avenir) ; Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Université Catholique de Louvain = Catholic University of Louvain (UCL) | Centre d'infectiologie Necker-Pasteur [CHU Necker] ; Institut Pasteur [Paris] (IP)-Hôpital Necker - Enfants Malades [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Service de Chirurgie ; Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION) | Agence Nationale de la Recherche [ANR-MIE 2008 N1R08063AS]; INSERM; CNRS; Universite de la Mediterranee; Region Provence Alpes Cote d'Azur; Institut National pour la Sante et la Recherche Medicale
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Show more [+] Less [-]English. The gut is a major barrier against microbes and encloses various innate lymphoid cells (ILCs), including two subsets expressing the natural cytotoxicity receptor NKp46. A subset of NKp46(+) cells expresses retinoic acid receptor-related orphan receptor γt (RORγt) and produces IL-22, like lymphoid tissue inducer (LTi) cells. Other NKp46(+) cells lack RORγt and produce IFN-γ, like conventional Natural Killer (cNK) cells. The identity, the regulation and the in vivo functions of gut NKp46(+) ILCs largely remain to be unravelled. Using pan-genomic profiling, we showed here that small intestine (SI) NKp46(+)RORγt(-) ILCs correspond to SI NK cells. Conversely, we identified a transcriptional programme conserved in fetal LTi cells and adult SI NKp46(+)RORγt(+) and NKp46(-)RORγt(+) ILCs. We also demonstrated that the IL-1β/IL-1R1/MyD88 pathway, but not the commensal flora, drove IL-22 production by NKp46(+)RORγt(+) ILCs. Finally, oral Listeria monocytogenes infection induced IFN-γ production in SI NK and IL-22 production in NKp46(+)RORγt(+) ILCs, but only IFN-γ contributed to control bacteria dissemination. NKp46(+) ILC heterogeneity is thus associated with subset-specific transcriptional programmes and effector functions that govern their implication in gut innate immunity.
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