Publication: Identity, regulation and in vivo function of gut NKp46(+)RORγt(+) and NKp46(+)RORγt(-) lymphoid cells.

Publié dans: EMBO Journal, 2011, 30 (14), pp.2934-47. ⟨10.1038/emboj.2011.201⟩

Auteurs: Ana Reynders, Nadia Yessaad, Thien-Phong Vu Manh, Marc Dalod, Aurore Fenis, Camille Aubry, Georgios Nikitas, Bertrand Escalière, Jean Christophe Renauld, Olivier Dussurget, Pascale Cossart, Marc Lecuit, Eric Vivier, Elena Tomasello

Résumé

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.

Lien vers Pubmed [PMID] – 21685873

Lien vers HAL – hal-00611641

Lien vers le DOI – 10.1038/emboj.2011.201