Abstract：
Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by diverse clinical manifestations and organ damage. Despite its elusive etiology, dysregulated subsets and functions of B cells are pivotal in SLE pathogenesis. Peoniflorin-6\'-O-benzene sulfonate (CP-25), an esterification modification of Paeoniflorin, exhibits potent anti-inflammatory and immunomodulatory properties in autoimmune diseases (AID). However, the involvement of CP-25 and its target, GRK2, in SLE development has not been explored. In this study, we demonstrate that both genetic deficiency and pharmacological inhibition of GRK2 attenuate autoantibodies production, reduce systemic inflammation, and mitigate histopathological alterations in the spleen and kidney in the pristane-induced mouse SLE model. Importantly, our findings highlight that both genetic deficiency and pharmacological inhibition of GRK2 suppress plasma cells generation and restore dysregulated B-cell subsets by modulating two crucial transcription factors, Blimp1 and IRF4. Collectively, targeting GRK2 with CP-25 emerges as a promising therapeutic approach for SLE.
摘要：
系统性红斑狼疮（SLE）是一种多方面的自身免疫性疾病，其特征是临床表现和器官损害多样。尽管病因难以捉摸，B细胞亚群和功能失调在SLE发病机制中至关重要。芍药苷-6'-O-苯磺酸盐(CP-25)，芍药苷的酯化改性，在自身免疫性疾病（AID）中表现出有效的抗炎和免疫调节特性。然而,CP-25及其目标的参与，GRK2，在SLE的发展还没有被探索。在这项研究中,我们证明GRK2的遗传缺陷和药理学抑制都会减弱自身抗体的产生，减少全身性炎症，并减轻普利烷诱导的小鼠SLE模型中脾脏和肾脏的组织病理学改变。重要的是,我们的研究结果强调，遗传缺陷和药物抑制GRK2抑制浆细胞生成和恢复失调的B细胞亚群通过调节两个关键的转录因子，Blimp1和IRF4。总的来说，CP-25靶向GRK2是一种有前途的SLE治疗方法.
