Abstract
Here we identified a population of bone marrow neutrophils that constitutively expressed the transcription factor RORγt and produced and responded to interleukin 17A (IL-17A (IL-17)). IL-6, IL-23 and RORγt, but not T cells or natural killer (NK) cells, were required for IL-17 production in neutrophils. IL-6 and IL-23 induced expression of the receptors IL-17RC and dectin-2 on neutrophils, and IL-17RC expression was augmented by activation of dectin-2. Autocrine activity of IL-17A and its receptor induced the production of reactive oxygen species (ROS), and increased fungal killing in vitro and in a model of Aspergillus-induced keratitis. Human neutrophils also expressed RORγt and induced the expression of IL-17A, IL-17RC and dectin-2 following stimulation with IL-6 and IL-23. Our findings identify a population of human and mouse neutrophils with autocrine IL-17 activity that probably contribute to the etiology of microbial and inflammatory diseases.
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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Animals
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Aspergillosis / complications
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Aspergillosis / immunology*
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Aspergillus / immunology*
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Autocrine Communication
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Bone Marrow Cells / immunology
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Cell Degranulation
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Cells, Cultured
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Cytotoxicity, Immunologic / genetics
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Disease Models, Animal
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Humans
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Interleukin-17 / genetics
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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-6 / immunology
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Keratitis / etiology
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Keratitis / immunology*
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Lectins, C-Type / genetics
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Lectins, C-Type / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neutrophils / immunology*
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Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
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Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
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Reactive Oxygen Species / metabolism
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Receptors, Interleukin / metabolism*
Substances
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IL17RC protein, human
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Il17rc protein, mouse
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Interleukin-17
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Interleukin-23
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Interleukin-6
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Lectins, C-Type
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Reactive Oxygen Species
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Receptors, Interleukin
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dectin-2, mouse