Pathogenic conversion of regulatory B10 cells into osteoclast-priming cells in rheumatoid arthritis. (January 2017)

• Record Type: Journal Article
• Authors: Hu, Fanlei; Liu, Hongjiang; Liu, Xu; Zhang, Xia; Xu, Liling; Zhu, Huaqun; Li, Yingni; Shi, Lianjie; Ren, Limin; Zhang, Jian; Li, Zhanguo; Jia, Yuan
• Is Part Of: Journal of autoimmunity. Volume 76(2017)
• Page Start: 53
• Page End: 62
• Publication Date: 2017-01
• Subjects: Rheumatoid arthritis -- Regulatory B10 cells -- Osteoclasts -- RANKL; RA rheumatoid arthritis -- RANKL receptor activator of NF-κB ligand -- OPG osteoprotegerin -- TNF tumor necrosis factor -- AIDs autoimmune diseases -- PB peripheral blood -- SF synovial fluid -- CIA collagen-induced arthritis; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2016.09.002
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Regulatory B10 cells were functionally impaired in rheumatoid arthritis (RA), yet the mechanisms were unclear. B cells are recently recognized as important participants in osteoclastogenesis by producing RANKL. In this study, we investigated whether regulatory B10 cells could convert into RANKL-producing cells, thus impairing their immunosuppressive functions in RA and exacerbating the disease progression. Our results showed that human regulatory B10 cells could ectopically express RANKL. Under RA circumstance, RANKL-producing B10 cells expanded dramatically, partially induced by TNF-α. The frequencies of these cells were positively correlated with RA patient disease activities and tender joint counts, but negatively correlated with the frequencies of regulatory B10 cells. Strikingly, RANKL-producing B10 cells from RA patients, but not healthy individuals significantly promoted osteoclast differentiation and bone erosion in a paracrine and cell-cell contact-dependent manner. Moreover, these pathogenic RANKL-producing B10 cells declined while regulatory IL-10-producing B10 cells increased in RA patients with disease remission after therapy. Collectively, these results showed that in RA, regulatory B10 cells demonstrated the potential of converting into RANKL-producing cells, thus exacerbating osteoclast formation, bone destruction and disease progression. Modulating the status of B10 cells might provide novel therapeutic strategies for RA. Highlights: Regulatory B10 cells were functionally impaired in RA patients . Under RA circumstance, regulatory B10 cells demonstrated the potential of converting into RANKL-producing cells . RANKL-producing B10 cells expanded dramatically in RA patients and were positively correlated with the disease activities . RANKL-producing B10 cells from RA patients significantly promoted osteoclast differentiation and bone erosion . RANKL-producing B10 cells declined while regulatory B10 cells increased in RA patients with remission after therapy .