title: CD147 modulates the differentiation of T-helper 17 cells in patients with rheumatoid arthritis.
abstract: The role of CD147 in regulation of rheumatoid arthritis (RA) is not fully elucidated. The aim of this study was to investigate the effect of cell-to-cell contact of activated CD14+monocytes with CD4+T cells, and the modulatory role of CD147 on T-helper 17 (Th17) cells differentiation in patients with RA. Twenty confirmed active RA patients and twenty normal controls were enrolled. CD4+T cells and CD14+monocytes were purified by magnetic beads cell sorting. Cells were cultured under different conditions in CD4+T cells alone, direct cell-to-cell contact co-culture of CD4+and CD14+cells, or indirect transwell co-culture of CD4+/CD14+cells in response to LPS and anti-CD3 stimulation with or without anti-CD147 antibody pretreatments. The proportion of IL-17-producing CD4+T cells (defined as Th17 cells) was determined by flow cytometry. The levels of interleukin (IL)-17, IL-6, and IL-1β in the supernatants of cultured cells were measured by ELISA. The optimal condition for in vitro induction of Th17 cells differentiation was co-stimulation with 0.1 μg/mL of LPS and 100 ng/mL of anti-CD3 for 3 days under direct cell-to-cell contact co-culture of CD4+and CD14+cells. Anti-CD147 antibody reduced the proportion of Th17 cells, and also inhibited the productions of IL-17, IL-6, and IL-1β in PBMC culture from RA patients. The current results revealed that Th17 differentiation required cell-to-cell contact with activated monocytes. CD147 promoted the differentiation of Th17 cells by regulation of cytokine production, which provided the evidence for pathogenesis and potential therapeutic targets for RA.
authors.affiliation: Department of Immunology and Rheumatology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology and Rheumatology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology and Rheumatology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Zhen-Jie
authors.initials: ZJ
authors.lastname: Yin
authors.affiliation: Department of Immunology and Rheumatology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Lv
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Department of Immunology and Rheumatology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D051926:Basigin / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D058504:Th17 Cells / Q000502:physiology*; D055815:Young Adult
chemical_list: C497886:BSG protein, human; D003470:Culture Media; D016207:Cytokines; D051926:Basigin
keywords: CD147; Rheumatoid arthritis; Th17 cells; monocytes; pathogenesis