系统性红斑狼疮
TLR7型
自身抗体
免疫系统
体外
B细胞激活因子
B细胞
炎症
狼疮性肾炎
免疫学
Toll样受体
生物
红斑狼疮
CD80
抗体
CD86
自身免疫
医学
T细胞
细胞生物学
先天免疫系统
内科学
疾病
生物化学
作者
Zhimiao Zou,Dunfeng Du,Miao Yan,Yang Yang,Yalong Xie,Zeyang Li,Liang Zhou,Limin Zhang,Ping Zhou,Fan Jiang
标识
DOI:10.1016/j.intimp.2020.106648
摘要
B cell hyperactivities are involved in the development of systemic lupus erythematosus (SLE). Toll-like receptor 7 (TLR7) in the B cells plays a pivotal role in the pathogenesis of SLE. Previous studies have focused on the intrinsic role of B cells in TLR7/MyD88 signaling and consequently on immune activation, autoantibody production, and systemic inflammation. However, a feasible treatment for this immune disorder remains to be discovered. The in vitro cellular response that have been studied likely plays a central role in the production of some important autoantibodies in SLE. We successfully used R848 to build a lupus-like B cell model in vitro; these B cells were overactivated, differentiated into plasma cells, escaped apoptosis, massively proliferated, and produced large amounts of autoantibodies and cytokines. In the present study, we found that TJ-M2010-5, a novel MyD88 inhibitor previously synthesized in our lab, seemed to inhibit the lupus-like condition of B cells, including overactivation, massive proliferation, differentiation into plasma cells, and overproduction of autoantibodies and cytokines. TJ-M2010-5 also induce B cells apoptosis. Furthermore, TJ-M2010-5 was found to remarkably inhibit NF-κB and MAPK signaling. In summary, TJ-M2010-5 might correct R848-induced lupus-like immune disorders of B cells by blocking the TLR7/MyD88/NF-κB and TLR7/MyD88/MAPK signaling pathways.
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