Abstract
Innate lymphoid cells (ILCs) are effectors of innate immunity and regulators of tissue modeling. Recently identified ILC populations have a cytokine expression pattern that resembles that of the helper T cell subsets T(H)2, T(H)17 and T(H)22. Here we describe a distinct ILC subset similar to T(H)1 cells, which we call 'ILC1'. ILC1 cells expressed the transcription factor T-bet and responded to interleukin 12 (IL-12) by producing interferon-γ (IFN-γ). ILC1 cells were distinct from natural killer (NK) cells as they lacked perforin, granzyme B and the NK cell markers CD56, CD16 and CD94, and could develop from RORγt(+) ILC3 under the influence of IL-12. The frequency of the ILC1 subset was much higher in inflamed intestine of people with Crohn's disease, which indicated a role for these IFN-γ-producing ILC1 cells in the pathogenesis of gut mucosal inflammation.
MeSH terms
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Animals
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CD56 Antigen / analysis
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Cell Differentiation
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Cells, Cultured
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Colitis / immunology
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Crohn Disease / immunology*
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Cytokines / immunology
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Cytokines / metabolism
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Granzymes / analysis
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Humans
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Inflammation
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Interferon-gamma / biosynthesis
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Interleukin-12 / metabolism*
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / metabolism
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Intestines / immunology
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Killer Cells, Natural / immunology
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Lymphocyte Subsets / immunology*
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Lymphocyte Subsets / metabolism
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Lymphocytes / immunology*
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Lymphocytes / metabolism
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Mice
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NK Cell Lectin-Like Receptor Subfamily D / analysis
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Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
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Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
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Perforin / analysis
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Receptors, IgG / analysis
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T-Box Domain Proteins / biosynthesis*
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Th1 Cells / immunology
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Th1 Cells / metabolism
Substances
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CD56 Antigen
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Cytokines
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NK Cell Lectin-Like Receptor Subfamily D
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, IgG
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Perforin
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Interleukin-12
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Interferon-gamma
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Granzymes