Identity, regulation and in vivo function of gut NKp46+ROR?t+ and NKp46+ROR?t- 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 ?t (ROR?t) and produces IL-22, like lymphoid tissue inducer (LTi) cells. Other NKp46(+) cells lack ROR?t and produce IFN-?, 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(+)ROR?t(-) ILCs correspond to SI NK cells. Conversely, we identified a transcriptional programme conserved in fetal LTi cells and adult SI NKp46(+)ROR?t(+) and NKp46(-)ROR?t(+) ILCs. We also demonstrated that the IL-1?/IL-1R1/MyD88 pathway, but not the commensal flora, drove IL-22 production by NKp46(+)ROR?t(+) ILCs. Finally, oral Listeria monocytogenes infection induced IFN-? production in SI NK and IL-22 production in NKp46(+)ROR?t(+) ILCs, but only IFN-? 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.

SUBMITTER: Reynders A 

PROVIDER: S-EPMC3160256 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature