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

Abstract

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. © 2011 European Molecular Biology Organization | All Rights Reserved.