Abstract
Interleukin 17 (IL-17)-producing CD4(+) helper T cells (T(H)-17 cells) have been linked to host defense and autoimmune diseases. In mice, the differentiation of T(H)-17 cells requires transforming growth factor-beta and IL-6 and the transcription factor RORgammat. We report here that for human naive CD4(+) T cells, RORgammat expression and T(H)-17 polarization were induced by IL-1beta and enhanced by IL-6 but were suppressed by transforming growth factor-beta and IL-12. Monocytes and conventional dendritic cells, but not monocyte-derived dendritic cells activated by microbial stimuli, efficiently induced T(H)-17 priming, and this function correlated with antigen-presenting cell production of IL-1beta and IL-6 but not IL-12. Our results identify cytokines, antigen-presenting cells and microbial products that promote the polarization of human T(H)-17 cells and emphasize an important difference in the requirements for the differentiation of T(H)-17 cells in humans and mice.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigen-Presenting Cells / immunology
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Cell Differentiation / immunology*
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Cell Lineage / immunology
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Cells, Cultured
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Cytokines / immunology
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Cytokines / metabolism
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Humans
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Interleukin-12 / metabolism
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Interleukin-17 / biosynthesis
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Interleukin-1beta / metabolism*
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Interleukin-6 / metabolism*
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Retinoic Acid / metabolism
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Receptors, Thyroid Hormone / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocyte Subsets / cytology*
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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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Transforming Growth Factor beta / metabolism*
Substances
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Cytokines
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Interleukin-17
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Interleukin-1beta
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Interleukin-6
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Nuclear Receptor Subfamily 1, Group F, Member 3
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RORC protein, human
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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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Transforming Growth Factor beta
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Interleukin-12