Identity, regulation and in vivo function of gut NKp46+RORγt+ and NKp46+RORγt- lymphoid cells

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 gamma t (ROR gamma t) and produces IL-22, like lymphoid tissue inducer (LTi) cells. Other NKp46(+) cells lack RORgt and produce IFN-gamma, 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 pangenomic profiling, we showed here that small intestine (SI) NKp46(+)ROR gamma t(-) ILCs correspond to SI NK cells. Conversely, we identified a transcriptional programme conserved in fetal LTi cells and adult SI NKp46(+)ROR gamma t(+) and NKp46(-)ROR gamma t(+) ILCs. We also demonstrated that the IL-1 beta/IL-1R1/MyD88 pathway, but not the commensal flora, drove IL-22 production by NKp46(+)ROR gamma t(+) ILCs. Finally, oral Listeria monocytogenes infection induced IFN-gamma production in SI NK and IL-22 production in NKp46(+)ROR gamma t(+) ILCs, but only IFN-gamma 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. The EMBO Journal ( 2011) 30, 2934-2947. doi:10.1038/emboj.2011.201; Published online 17 June 2011