Jing Zhang, Xiaoxi Hu, Xiaojie Dong, Wensheng Chen, Lingling Zhang, Yan Chang, Yujing Wu, Wei Wei
Frontiers in immunology 2020Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and T cell hyper-activation. Emerging evidence has shown that the stimulation of immunoglobulin D (IgD) induces T cell activation and may contribute to disease pathogenesis. In this study, the sIgD concentrations were positively associated with disease activity score in 28 joints (DAS28) and anti-cyclic citrullinated peptide (anti-CCP) in RA. We demonstrated that IgD-Fc-Ig (composed of human IgD Fc domain and IgG1 Fc domain, obtained through prokaryotic protein expression and chromatography purification) effectively inhibited the activation and proliferation of T cells in healthy controls and PBMCs in RA patients stimulated by IgD, recovered the Th17/Treg cell subset balance, and downregulated p-Lck and p-ZAP70 expression. Moreover, in vivo, IgD-Fc-Ig decreased the swollen joint counts and arthritis indices in mice with collagen-induced arthritis (CIA), and ameliorated histopathological changes in joint and spleen tissue. It also downregulated thymocyte proliferation and reduced the percentage of helper T cells (Th) and CD154+ T cells, reversed the imbalance of Th1/Th2 and Th17/Treg cell subsets, reduced cytokine and chemokine levels, and inhibited p-Lck and p-ZAP70 expression. Our data suggest that IgD-Fc-Ig fusion protein regulates T> cell activity in RA. These findings have potential implications for IgD-targeted strategies to treat IgD-associated RA. Copyright © 2020 Zhang, Hu, Dong, Chen, Zhang, Chang, Wu and Wei.
Jing Zhang, Xiaoxi Hu, Xiaojie Dong, Wensheng Chen, Lingling Zhang, Yan Chang, Yujing Wu, Wei Wei. Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig. Frontiers in immunology. 2020;11:755
PMID: 32499775
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