Journal of Immunology Research, 2014-01, Vol.2014, p.385352-12
2014
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Details
- Autor(en) / Beteiligte
- Titel
- TNFα Promotes Th17 Cell Differentiation through IL-6 and IL-1β Produced by Monocytes in Rheumatoid Arthritis
- Ist Teil von
- Journal of Immunology Research, 2014-01, Vol.2014, p.385352-12
- Ort / Verlag
- Egypt: Hindawi Publishing Corporation
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- TNFα plays an important role in autoimmune pathogenesis and is the main therapeutic target of rheumatoid arthritis. However, its underlying mechanism is not completely understood. In this study, we described that Th17 cells were accumulated in synovial fluid, which was attributable to TNFα aberrantly produced in rheumatoid synovium. Interestingly, TNFα cannot induce IL-17 production of CD4+ T cells directly, but through the monocytes high levels of IL-1β and IL-6 in a TNFRI and TNFRII dependent manner from the active RA patients are produced. TNFα was shown to enhance the phosphorylation level of STAT3 and the expression level of transcription factor RORC of CD4+ T cells when cultured with CD14+ monocytes. Treatment with an approved TNFα blocking antibody showed marked reduction in the levels of IL-6, IL-1β, and IL-17 and the expression level of STAT3 phosphorylation in relation to Th17 cell differentiation in patients with rheumatoid arthritis. The study provides new evidence supporting the critical role of TNFα in the pathogenic Th17 cell differentiation in rheumatoid arthritis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2314-8861eISSN: 2314-7156DOI: 10.1155/2014/385352Titel-ID: cdi_doaj_primary_oai_doaj_org_article_122024731b944e3d88b97bd56385231d
- Format
- –
- Schlagworte
- Aged, Antibodies, Blocking - immunology, Antibodies, Blocking - pharmacology, Antibodies, Monoclonal - therapeutic use, Antirheumatic Agents - therapeutic use, Arthritis, Rheumatoid - blood, Arthritis, Rheumatoid - drug therapy, Arthritis, Rheumatoid - immunology, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - metabolism, Cell differentiation, Cell Differentiation - drug effects, Cell Differentiation - immunology, Cells, Cultured, Development and progression, Female, Genetic aspects, Health aspects, Humans, Immunoblotting, Infliximab, Interleukin-1beta - immunology, Interleukin-1beta - metabolism, Interleukin-6 - immunology, Interleukin-6 - metabolism, Male, Middle Aged, Monocytes - immunology, Monocytes - metabolism, Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics, Nuclear Receptor Subfamily 1, Group F, Member 3 - immunology, Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism, Phosphorylation - immunology, Physiological aspects, Receptors, Tumor Necrosis Factor, Type I - immunology, Receptors, Tumor Necrosis Factor, Type I - metabolism, Receptors, Tumor Necrosis Factor, Type II - immunology, Receptors, Tumor Necrosis Factor, Type II - metabolism, Reverse Transcriptase Polymerase Chain Reaction, Rheumatoid arthritis, STAT3 Transcription Factor - immunology, STAT3 Transcription Factor - metabolism, Synovial Fluid - cytology, Synovial Fluid - immunology, Synovial Fluid - metabolism, T cells, Th17 Cells - drug effects, Th17 Cells - immunology, Th17 Cells - metabolism, Tumor necrosis factor, Tumor Necrosis Factor-alpha - antagonists & inhibitors, Tumor Necrosis Factor-alpha - immunology, Tumor Necrosis Factor-alpha - metabolism