Identity, regulation andin vivofunction 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.