Abstract
Interleukin 22 (IL-22) is a member of the IL-10 cytokine family that is involved in inflammatory and wound healing processes. Originally considered a T helper type 1 (T(H)1)-associated cytokine, IL-22 has since been shown to be produced mainly by IL-17-producing helper T cells (T(H)-17 cells). Here we describe a previously uncharacterized IL-22-producing human helper T cell population that coexpressed the chemokine receptor CCR6 and the skin-homing receptors CCR4 and CCR10. These cells were distinct from both T(H)-17 cells and T(H)1 cells. Downregulation of either the aryl hydrocarbon receptor (AHR) or the transcription factor RORC by RNA-mediated interference affected IL-22 production, whereas IL-17 production was affected only by downregulation of RORC by RNA-mediated interference. AHR agonists substantially altered the balance of IL-22- versus IL-17-producing cells. This subset of IL-22-producing cells may be important in skin homeostasis and pathology.
MeSH terms
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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Cell Differentiation
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Down-Regulation
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Humans
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Immunologic Memory
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Interferon-gamma / biosynthesis
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Interleukin-13 / biosynthesis
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Interleukin-17 / biosynthesis
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Interleukin-22
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Interleukins / biosynthesis*
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Lymphocyte Activation
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Aryl Hydrocarbon / agonists
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Receptors, Aryl Hydrocarbon / physiology
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Receptors, CCR10 / biosynthesis
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Receptors, CCR4 / biosynthesis
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Receptors, CCR6 / biosynthesis
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Receptors, Retinoic Acid / physiology
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Receptors, Thyroid Hormone / physiology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism*
Substances
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CCR10 protein, human
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CCR4 protein, human
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CCR6 protein, human
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Interleukin-13
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Interleukin-17
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Interleukins
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Nuclear Receptor Subfamily 1, Group F, Member 3
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RORC protein, human
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Receptors, Aryl Hydrocarbon
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Receptors, CCR10
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Receptors, CCR4
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Receptors, CCR6
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Interferon-gamma