Abstract
Interleukin 22 (IL-22) is a cytokine produced by the T(H)-17 lineage of helper T cells and NK-22 subset of natural killer cells that acts on epithelial cells and keratinocytes and has been linked to skin homeostasis and inflammation. Here we characterize a population of human skin-homing memory CD4(+) T cells that expressed the chemokine receptors CCR10, CCR6 and CCR4 and produced IL-22 but neither IL-17 nor interferon-gamma (IFN-gamma). Clones isolated from this population produced IL-22 only and had low or undetectable expression of the T(H)-17 and T helper type 1 (T(H)1) transcription factors RORgammat and T-bet. The differentiation of T cells producing only IL-22 was efficiently induced in naive T cells by plasmacytoid dendritic cells in an IL-6- and tumor necrosis factor-dependent way. Our findings delineate a previously unknown subset of human CD4(+) effector T cells dedicated to skin pathophysiology.
Publication types
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Research Support, Non-U.S. Gov't
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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Humans
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Immunologic Memory
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In Vitro Techniques
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Interleukin-17 / biosynthesis*
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Interleukin-22
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Interleukins / biosynthesis*
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, CCR10 / metabolism
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Receptors, CCR4 / metabolism
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Receptors, CCR6 / metabolism
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Receptors, Retinoic Acid / metabolism
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Receptors, Thyroid Hormone / metabolism
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Skin / immunology*
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T-Box Domain Proteins / metabolism
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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-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, 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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T-Box Domain Proteins
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T-box transcription factor TBX21