Abstract
Th17 cells require IL-6 and TGFbeta for lineage commitment and IL-23 for maintenance. Unexpectedly, naive IL-6(-/-) splenocytes stimulated with anti-CD3 and IL-23 produced normal amounts of IL-17 during the first 24 h of culture. These rapid IL-6-independent IL-17 producers were identified as predominantly DX5(+) TCRbeta(+) NKT cells, and a comparable response could be found using the invariant NKT-specific ligand alpha-galactosylceramide. Human NKT cells also produced IL-17. NKT cells constitutively expressed IL-23R and RORgammat. Ligation of either TCR or IL-23R triggered IL-17 production and both together had a synergistic effect, suggesting independent but convergent pathways. IL-17 production was not restricted to a particular subset of NKT cells but they were NK1.1 negative. Importantly, in vivo administration of alpha-galactosylceramide triggered a rapid IL-17 response in the spleen. These data suggest an important biological role for innate IL-17 production by NKT cells that is rapid and precedes the adaptive IL-17 response.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Humans
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Immunity, Innate
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Interleukin-17 / immunology
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Interleukin-17 / metabolism*
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Interleukin-23 / immunology
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Interleukin-23 / metabolism
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Interleukin-6 / immunology
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Interleukin-6 / metabolism
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Mice
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Mice, Inbred C57BL
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Interleukin / immunology
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Receptors, Interleukin / 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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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
Substances
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Interleukin-17
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Interleukin-23
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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, Antigen, T-Cell
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Receptors, Interleukin
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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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interleukin-23 receptor, mouse