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Identity, regulation and in vivo function of gut NKp46 + RORγt + and NKp46 + RORγt − lymphoid cells
Author(s) -
Reynders Ana,
Yessaad Nadia,
Vu Manh ThienPhong,
Dalod Marc,
Fenis Aurore,
Aubry Camille,
Nikitas Georgios,
Escalière Bertrand,
Renauld Jean Christophe,
Dussurget Olivier,
Cossart Pascale,
Lecuit Marc,
Vivier Eric,
Tomasello Elena
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.201
Subject(s) - innate lymphoid cell , rar related orphan receptor gamma , biology , orphan receptor , immunology , microbiology and biotechnology , transcription factor , immunity , immune system , genetics , foxp3 , gene
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.