Abstract
The interleukin (IL) 17 family of cytokines has emerged to be critical for host defense as well as the pathogenesis of autoimmune and autoinflammatory disorders, and serves to link adaptive and innate responses. Recent studies have identified a new subset of T cells that selectively produce IL-17 (Th17 cells; Bettelli, E., T. Korn, and V.K. Kuchroo. 2007. Curr. Opin. Immunol. 19:652-657; Kolls, J.K., and A. Linden. 2004. Immunity. 21:467-476), but the regulation of IL-17 production by innate immune cells is less well understood. We report that in vitro stimulation with IL-23 induced IL-17 production by recombination activating gene (Rag) 2(-/-) splenocytes but not Rag2(-/-) common gamma chain(-/-) splenocytes. We found that a major source of IL-17 was CD4(+)CD3(-)NK1.1(-)CD11b(-)Gr1(-)CD11c(-)B220(-) cells, a phenotype that corresponds to lymphoid tissue inducer-like cells (LTi-like cells), which constitutively expressed the IL-23 receptor, aryl hydrocarbon receptor, and CCR6. In vivo challenge with the yeast cell wall product zymosan rapidly induced IL-17 production in these cells. Genetic deletion of signal transducer and activator of transcription 3 reduced but did not abrogate IL-17 production in LTi-like cells. Thus, it appears that splenic LTi-like cells are a rapid source of IL-17 and IL-22, which might contribute to dynamic organization of secondary lymphoid organ structure or host defense.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Antigens, CD / analysis
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CD4 Antigens / analysis
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Cells, Cultured
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DNA-Binding Proteins / genetics
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Flow Cytometry
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Gene Expression / drug effects
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Immune System / cytology
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Immune System / metabolism*
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Immunity, Innate / immunology*
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Interleukin Receptor Common gamma Subunit / genetics
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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-22
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Interleukin-23 / pharmacology
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Interleukins / genetics
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Interleukins / immunology
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Interleukins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Aryl Hydrocarbon / genetics
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Receptors, CCR6 / genetics
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Receptors, Interleukin / genetics
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Receptors, Retinoic Acid / genetics
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Receptors, Thyroid Hormone / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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STAT3 Transcription Factor / genetics
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Spleen / cytology
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Spleen / metabolism
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Zymosan / pharmacology
Substances
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Antigens, CD
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CCR6 protein, mouse
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CD4 Antigens
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DNA-Binding Proteins
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Interleukin Receptor Common gamma Subunit
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Interleukin-17
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Interleukin-23
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Interleukins
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Rag2 protein, mouse
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Receptors, Aryl Hydrocarbon
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Receptors, CCR6
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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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STAT3 Transcription Factor
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Stat3 protein, mouse
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interleukin-23 receptor, mouse
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Zymosan