Identity, regulation and in vivo function of gut NKp46(+)RORγt(+) and NKp46(+)RORγt(-) lymphoid cells.
(2011) The EMBO journal — Vol. 30, n° 14, p. 2934-2947 (2011)
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- 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.
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Reynders, A., Yessaad, N., Vu Manh, T.-P., Dalod, M., Fenis, A., Aubry, C., Nikitas, G., Renauld, J.-C., Dussurget, O., Cossart, P., Lecuit, M., Vivier, E., & Tomasello, E. (2011). Identity, regulation and in vivo function of gut NKp46(+)RORγt(+) and NKp46(+)RORγt(-) lymphoid cells. The EMBO journal, 30(14), 2934-2947. https://doi.org/10.1038/emboj.2011.201 (Original work published 2011)