title: TNFα promotes Th17 cell differentiation through IL-6 and IL-1β produced by monocytes in rheumatoid arthritis.
abstract: 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.
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China ; Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Guanghua Integrative Medicine Hospital, 540 Xinhua Road, Shanghai 200052, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Guanghua Integrative Medicine Hospital, 540 Xinhua Road, Shanghai 200052, China ; Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, 540 Xinhua Road, Shanghai 200052, China.
authors.forename: Dongyi
authors.initials: D
authors.lastname: He
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Hong
authors.identifier: 0000-0002-0038-6543
authors.initials: H
authors.lastname: Nie
mesh_terms: D000368:Aged; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015151:Immunoblotting; D000069285:Infliximab; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab