title: Preferential Induction of the T Cell Auxiliary Signaling Molecule B7-H3 on Synovial Monocytes in Rheumatoid Arthritis.
abstract: B7-H3, a newly identified B7 family member, has functional duality as a co-stimulator and co-inhibitor that fine-tunes T cell-mediated immune responses. Given that B7-H3 expression on human monocytes and dendritic cells is enhanced by inflammatory cytokines, its potential inmmunoregulatory role at sites of inflammation has been suggested. Further, monocytes play crucial roles in the pathophysiology of various inflammatory disorders including autoimmune diseases; however, the immunological role of B7-H3 in rheumatoid arthritis (RA) has not been defined. Thus, we aimed to investigate the possible roles of monocyte B7-H3 in the pathogenesis of RA. Synovial monocytes, but not peripheral monocytes, in RA patients predominantly express surface B7-H3. The 4Ig isoform of B7-H3 is exclusively induced on the cell surface, whereas the 2Ig B7-H3 isoform is constitutively expressed in the intracytoplasmic region of both peripheral and synovial monocytes. B7-H3 knockdown experiments reveal that surface B7-H3 has an inhibitory effect on IFN-γ production in CD4 memory cells. Moreover, surface B7-H3 expression on synovial monocytes inversely correlates with RA clinical parameters. Our findings demonstrate that activation-induced B7-H3 expression on synovial monocytes has the potential to inhibit Th1-mediated immune responses and immunomodulatory roles affecting RA pathogenesis.
authors.affiliation: From the Departments of Microbiology and Immunology and.
authors.forename: Bo Ruem
authors.initials: BR
authors.lastname: Yoon
authors.affiliation: From the Departments of Microbiology and Immunology and the BK21Plus Biomedical Science Project, and the Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Yeon-Ho
authors.initials: YH
authors.lastname: Chung
authors.affiliation: the Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Yoo
authors.affiliation: From the Departments of Microbiology and Immunology and the Tokyo Medical and Dental University School of Medicine, Tokyo 113-8510, Japan, and.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawara
authors.affiliation: the Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
authors.forename: Jinhyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: the Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea.
authors.forename: In Seol
authors.initials: IS
authors.lastname: Yoo
authors.affiliation: From the Departments of Microbiology and Immunology and Biomedical Sciences and.
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.affiliation: the Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, South Korea, kangsw@cnuh.co.kr.
authors.forename: Seong Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: From the Departments of Microbiology and Immunology and the BK21Plus Biomedical Science Project, and the Seoul National University College of Medicine, Seoul 110-799, South Korea, Biomedical Sciences and the Cancer Research Institute, Ischemic/Hypoxic Disease Institute, and Institute of Infectious Diseases, Seoul National University College of Medicine, Seoul National University Hospital Biomedical Research Institute, Seoul 110-799, South Korea wonwoolee@snu.ac.kr.
authors.forename: Won-Woo
authors.initials: WW
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D060887:B7 Antigens / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D060887:B7 Antigens; C423237:CD276 protein, human; C573415:IFNG protein, human; D007371:Interferon-gamma
keywords: B7-H3; autoimmune disease; cellular immune response; immunoglobulin-like domain; inflammation; interferon-gamma; monocyte; rheumatoid arthritis; synovial fluid