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Microbial Flora Drives Interleukin 22 Production in Intestinal NKp46+ Cells that Provide Innate Mucosal Immune Defense

Abstract : Natural killer (NK) cells are innate lymphocytes with spontaneous antitumor activity, and they produce interferon-gamma (IFN-gamma) that primes immune responses. Whereas T helper cell subsets differentiate from naive T cells via specific transcription factors, evidence for NK cell diversification is limited. In this report, we characterized intestinal lymphocytes expressing the NK cell natural cytotoxicity receptor NKp46. Gut NKp46+ cells were distinguished from classical NK cells by limited IFN-gamma production and absence of perforin, whereas several subsets expressed the nuclear hormone receptor retinoic acid receptor-related orphan receptor t (RORgammat) and interleukin-22 (IL-22). Intestinal NKp46+IL-22+ cells were generated via a local process that was conditioned by commensal bacteria and required RORgammat. Mice lacking IL-22-producing NKp46+ cells showed heightened susceptibility to the pathogen Citrobacter rodentium, consistent with a role for intestinal NKp46+ cells in immune protection. RORgammat-driven diversification of intestinal NKp46+ cells thereby specifies an innate cellular defense mechanism that operates at mucosal surfaces.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01402754
Contributor : Bérengère Hugot <>
Submitted on : Friday, November 25, 2016 - 10:21:32 AM
Last modification on : Thursday, June 11, 2020 - 6:44:03 PM

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Naoko Satoh-Takayama, Christian A. J. Vosshenrich, Sarah Lesjean-Pottier, Shinichiro Sawa, Matthias Lochner, et al.. Microbial Flora Drives Interleukin 22 Production in Intestinal NKp46+ Cells that Provide Innate Mucosal Immune Defense. Immunity, Elsevier, 2008, 29 (6), pp.958 - 970. ⟨10.1016/j.immuni.2008.11.001⟩. ⟨pasteur-01402754⟩

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