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

Centre d'Immunologie de Marseille-Luminy, Université de la Mediterannée, Campus du Luminy, Marseille, France.
The EMBO Journal (Impact Factor: 10.43). 06/2011; 30(14):2934-47. DOI: 10.1038/emboj.2011.201
Source: PubMed


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.


Available from: Jean-Christophe Renauld
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    • "We also assessed the expression of transcription factors that are typically associated with Th1 (Tbet) and Th17 (RORγt) effectors (both in the conjunctiva and CLNs) and noted their significantly increased expression in the TSP-1 null conjunctiva at all ages while in CLNs after 8 weeks of age. However more recent reports indicate that in mucosal tissues NK cells or their subset are capable of expressing these transcription factors [38-40] although the presence of such a population in the conjunctiva is yet to be established. Since RORγt+ innate cells are rare in the peripheral lymph nodes our results suggest a more likely increase in Th1 and Th17 effectors in the CLNs of TSP-1 null mice, however a possible recruitment of NK cells to the draining lymph nodes as a part of an inflammatory response in these mice cannot be ruled out. "
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