Abstract
Recently, IL-17 produced by Th17 cells was described as pro-inflammatory cytokine with an eminent role in autoimmune diseases, e.g. rheumatoid arthritis. A lack of IL-17 leads to amelioration of collagen-induced arthritis. IL-17 induction in naïve CD4(+) T cells depends on IL-6 and TGF-beta and is enhanced by IL-23. The in vivo inflammatory potential of in vitro-primed Th17 cells however, remains unclear. Here, we show that, although IL-17 neutralisation results in amelioration of murine OVA-induced arthritis, in vitro-primed Th17 cells cannot exacerbate arthritic symptoms after adoptive transfer. Furthermore, Th17 cells cannot induce an inflammatory delayed type hypersensitivity reaction because they fail to migrate into inflamed sites, possibly due to the lack of CXCR3 expression. Also, re-isolated Th17 cells acquired IFN-gamma expression, indicating instability of the Th17 phenotype. Taken together, the data show that IL-6, TGF-beta and IL-23 might not provide sufficient signals to induce "fully qualified" Th17 cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Arthritis, Experimental / etiology
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Arthritis, Experimental / immunology*
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Arthritis, Experimental / pathology
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Cells, Cultured / immunology
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Cells, Cultured / transplantation
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Chemotaxis, Leukocyte*
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Disease Models, Animal
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Hypersensitivity, Delayed / immunology
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Hypersensitivity, Delayed / prevention & control
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Immunization
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Interleukin-17 / antagonists & inhibitors
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Interleukin-17 / immunology*
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Interleukin-23 / pharmacology
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Interleukin-6 / pharmacology
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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, SCID
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Mice, Transgenic
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Osteoarthritis, Knee / etiology
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Osteoarthritis, Knee / immunology*
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Osteoarthritis, Knee / pathology
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Ovalbumin / immunology
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Ovalbumin / toxicity
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Peptide Fragments / immunology
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Peptide Fragments / toxicity
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Receptors, CXCR3 / analysis
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / transplantation
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Transforming Growth Factor beta / pharmacology
Substances
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Cxcr3 protein, mouse
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Interleukin-17
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Interleukin-23
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Interleukin-6
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OVA 323-339
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Peptide Fragments
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Receptors, CXCR3
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Transforming Growth Factor beta
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Ovalbumin