Abstract
IL-33 has recently been identified as a cytokine endowed with pro-Th2 functions, raising the question of its effect on invariant natural killer T cell (iNKT), which are potent IL-4 producers. Here, we report a two-fold increase of iNKT-cell counts in spleen and liver after a 7-day treatment of mice with IL-33, which results from a direct effect, given that purified iNKT cells express the T1/ST2 receptor constitutively and respond to IL-33 by in vitro expansion and functional activation. Conversely to the expected pro-Th2 effect, IL-33 induced a preferential increase in IFN-gamma rather than IL-4 production upon TCR engagement that depended on endogenous IL-12. Moreover, in combination with the pro-inflammatory cytokine IL-12, IL-33 enhanced IFN-gamma production by both iNKT and NK cells. Taken together these data support the conclusion that IL-33 can contribute as a co-stimulatory factor to innate cellular immune responses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Female
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Humans
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Interferon-gamma / agonists
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Interferon-gamma / immunology
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Interferon-gamma / metabolism*
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Interleukin-12 / immunology
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Interleukin-12 / metabolism*
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Interleukin-33
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Interleukin-4 / agonists
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Interleukin-4 / immunology
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Interleukin-4 / metabolism
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Interleukins / immunology*
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Interleukins / pharmacology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Liver / drug effects
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Liver / immunology
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Liver / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Natural Killer T-Cells / drug effects
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Natural Killer T-Cells / immunology*
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Natural Killer T-Cells / metabolism
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Spleen / drug effects
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Spleen / immunology
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Spleen / metabolism
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Th2 Cells / drug effects
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Th2 Cells / immunology*
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Th2 Cells / metabolism
Substances
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IL33 protein, human
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Interleukin-33
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Interleukins
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Interleukin-12
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Interleukin-4
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Interferon-gamma