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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Ly / immunology*
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Antigens, Ly / metabolism
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Citrobacter rodentium / immunology*
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Enterobacteriaceae Infections / immunology*
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Enterobacteriaceae Infections / microbiology
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Immunity, Innate
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Immunity, Mucosal / immunology
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Interleukin-22
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Interleukins / immunology*
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Interleukins / metabolism
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Intestinal Mucosa / metabolism
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Intestines / immunology*
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Intestines / microbiology
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Natural Cytotoxicity Triggering Receptor 1 / immunology*
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Natural Cytotoxicity Triggering Receptor 1 / metabolism
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Perforin / immunology
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Perforin / metabolism
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Receptors, Retinoic Acid / immunology
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Receptors, Retinoic Acid / metabolism
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Receptors, Thyroid Hormone / immunology
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Receptors, Thyroid Hormone / metabolism
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Signal Transduction / immunology
Substances
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Antigens, Ly
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Interleukins
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Natural Cytotoxicity Triggering Receptor 1
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Ncr1 protein, mouse
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Rorc protein, mouse
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Perforin