Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis

• Main Authors: Xiao-Yu Cai, Yue Zhu, Chen Wang, Xiao-Yu Tang, Le Han, Jin-Ling Shu, Xian-Zheng Zhang, Fa-Qin Liang, Jing-Ru Ge, Li Xu, Dan Mei, Ling-Ling Zhang, Wei Wei
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-05-01
• Series: Frontiers in Pharmacology
• Subjects: rheumatoid arthritis; etanercept; TNF-α; B cell differentiation; NF-κB pathway
• Online Access: https://www.frontiersin.org/article/10.3389/fphar.2020.00676/full

ObjectiveTo explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells.MethodsIn RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB.ResultsThe percentage of CD19−CD27+CD138+ plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19+ total B cells, CD19+CD27+ memory B cells and CD19−CD27+CD138+ plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells.ConclusionB cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway.