TNFαPromotes Th17 Cell Differentiation through IL-6 and IL-1βProduced by Monocytes in Rheumatoid Arthritis

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Abstract
TNFαplays 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 TNFαaberrantly produced in rheumatoid synovium. Interestingly, TNFαcannot induce IL-17 production of CD4+T cells directly, but through the monocytes high levels of IL-1βand IL-6 in a TNFRI and TNFRII dependent manner from the active RA patients are produced. TNFαwas 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 TNFαblocking 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 TNFαin the pathogenic Th17 cell differentiation in rheumatoid arthritis.
Funding Information
  • National Natural Science Foundation of China (81273307, 81202351, 81072470, 30872304, 31270963, 81273979, 2014CB541803, 14ZZ106, 20114027)
  • National Natural Science Foundation of China (81273307, 81202351, 81072470, 30872304, 31270963, 81273979, 2014CB541803, 14ZZ106, 20114027)
  • National Natural Science Foundation of China (81273307, 81202351, 81072470, 30872304, 31270963, 81273979, 2014CB541803, 14ZZ106, 20114027)
  • National Natural Science Foundation of China (81273307, 81202351, 81072470, 30872304, 31270963, 81273979, 2014CB541803, 14ZZ106, 20114027)
  • National Natural Science Foundation of China (81273307, 81202351, 81072470, 30872304, 31270963, 81273979, 2014CB541803, 14ZZ106, 20114027)
  • National Natural Science Foundation of China (81273307, 81202351, 81072470, 30872304, 31270963, 81273979, 2014CB541803, 14ZZ106, 20114027)
  • National Basic Research Program of China (81273307, 81202351, 81072470, 30872304, 31270963, 81273979, 2014CB541803, 14ZZ106, 20114027)
  • Shanghai Municipal Education Commission (81273307, 81202351, 81072470, 30872304, 31270963, 81273979, 2014CB541803, 14ZZ106, 20114027)
  • Shanghai Municipal Health Bureau (81273307, 81202351, 81072470, 30872304, 31270963, 81273979, 2014CB541803, 14ZZ106, 20114027)

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