IL-17B and IL-17C Are Associated with TNF- Production and Contribute to the Exacerbation of Inflammatory Arthritis

Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
The Journal of Immunology (Impact Factor: 4.92). 12/2007; 179(10):7128-36. DOI: 10.4049/jimmunol.179.10.7128
Source: PubMed


IL-17A is a T cell-derived proinflammatory cytokine that contributes to the pathogenesis of rheumatoid arthritis. Recently, six related molecules have been identified to form the IL-17 family, as follows: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F. Whereas IL-17A and IL-17F up-regulate IL-6 in synovial fibroblasts, IL-17B and IL-17C are reported to stimulate the release of TNF-alpha and IL-1beta from the monocytic cell line, THP-1 cell. However, their detailed function remains to be elucidated. We report in this study the effects of IL-17 family on the collagen-induced arthritis (CIA) progression by T cell gene transfer and bone marrow chimeric mice. The mRNA expressions of IL-17 family (IL-17A, IL-17B, IL-17C, and IL-17F) and their receptor (IL-17R and IL-17Rh1) genes in the arthritic paws of CIA mice were elevated compared with controls. Although IL-17A and IL-17F were expressed in CD4(+) T cells, IL-17B and IL-17C were expressed in the cartilage and in various cell populations in the CIA arthritic paws, respectively. In vitro, IL-17A, IL-17B, IL-17C, and IL-17F induced TNF-alpha production in mouse peritoneal exudate cells. In vivo, adoptive transfer of IL-17B- and IL-17C-transduced CD4(+) T cells evidently exacerbated arthritis. Bone marrow chimeric mice of IL-17B and IL-17C exhibited elevated serum TNF-alpha concentration and the high arthritis score upon CIA induction. Moreover, neutralization of IL-17B significantly suppressed the progression of arthritis and bone destruction in CIA mice. Therefore, not only IL-17A, but also IL-17B and IL-17C play an important role in the pathogenesis of inflammatory arthritis.

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Available from: Nelson H Tsuno
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    • "Correspondingly, IL-25 plays distinct roles in immunity, mainly regulating the T helper (Th) 2 response against helminthic parasites and allergic inflammation.4,5,6 IL-17B, IL-17C and IL-17D have been shown to induce the production of pro-inflammatory cytokines, but their biological function is largely unknown.7,8,9,10 Recent studies by three different groups highlighted the function of IL-17C in mucosal immunity and autoimmune responses.11,12,13 "
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    • "Rorc mRNA encodes the transcription factor Rorγt, which is involved in the differentiation of CD4+ T cells to Th17 pro-inflammatory cells. The role of IL-17 in the pathogenesis of arthritis is well known and was first confirmed in the CIA model [53]. In agreement with the FACS results of CD8+ naïve T cells, we also found that the CIA-resistant DBA-2/J strain has diminished numbers of Rorγt+T cells in the periphery (Figure 9). "
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    • "IL-17B was recently identified to activate both TNF and NFkB pathways [25]. IL-17B-induced expression of TNF and IL-1β results in monocytic chemotaxis [26], a phenomenon that is well described in colorectal liver metastases [27,28]. "
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