AB0039 Preferential Induction of 4IG B7-H3 on Synovial Monocytes in Rheumatoid Arthritis (RA): Possible Role of 4IG B7-H3 as a Co-Inhibitory Ligand. (9th June 2015)

• Record Type: Journal Article
• Authors: Kang, S.W.; Yoon, B.R.; Yoo, S.-J.; Kim, J.; Yoo, I.S.; Lee, W.-W.
• Is Part Of: Annals of the rheumatic diseases. Volume 74(2015)Supplement 2
• Page Start: 903
• Page End: 903
• Publication Date: 2015-06-09
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2015-eular.3372
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: B7-H3 (B7-H3), newly identified B7 family member, has functional duality as a T-cell costimulator or coinhibitor for fine-tuning T-cell mediated immune responses. Given that B7-H3 expression is enhanced in human monocyte and dendritic cells by inflammatory cytokines, it has been suggested their potential inmmunoregulatory function at sites of inflammation. Monocytes play a crucial role 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. Objectives: We aimed to investigate the possible roles of B7-H3 on monocyte in pathogenesis of RA. Methods: Synovial fluid and peripheral blood from 33 RA patients and peripheral blood from 19 healthy controls (HCs) were obtained. The expression of B7-H3 on monocytes in RA patients and HCs were analyzed using flow cytometic analysis and quantitative RT-PCR. Purified synovial and peripheral monocytes were used for immunoblotting and intracellular flow cytometic analysis to investigate the distinct expression and localization of two isoforms of B7-H3. B7-H3-expressing THP-1 cells were transfected with B7-H3-specific siRNA and subjected to coculture assay with CD4 T cells. Proliferation and cytokine production of the cocultured T cells were assessed by CFSE dilution and ELISA, respectively. Clinical relevance of enhanced B7-H3 expression in RA was tested by comparison with clinical parameters and disease severity in the patients and with synovial cytokine levels measured by multiplex cytokine assay. Results: Synovial monocytes but not peripheral monocytes in RA patients predominantly induce surface B7-H3 expression. The induced B7-H3 is exclusively 4Ig isoform, whereas 2Ig B7-H3 isoform constitutively express the intracytoplasmic region both peripheral and synovial monocytes. The B7-H3 knockdown experiments provided the evidence that 4Ig B7-H3 isoform has an inhibitory effect on interferon-gamma (IFN-γ) production of CD4 memory cells. Moreover, the expression level of 4Ig B7-H3 on synovial monocytes was inversely correlated with clinical parameters such as C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and Disease Activity Score in 28 joints (DAS28). Conclusions: Our findings demonstrate that activation-induced B7-H3 expression on synovial monocytes has the potential to inhibit Th1-mediated immune response and immunomodulatory role affecting pathogenesis of RA. Disclosure of Interest: None declared