1. Inhibition of GRK2 ameliorates the pristane-induced mouse SLE model by suppressing plasma cells differentiation.
- Author
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Han D, Jiang C, Xu H, Chu R, Zhang R, Fang R, Ge H, Lu M, Wang M, Tai Y, Yan S, Wei W, and Wang Q
- Subjects
- Animals, Female, Mice, Anti-Inflammatory Agents pharmacology, Autoantibodies blood, Cell Differentiation drug effects, Glucosides pharmacology, Kidney pathology, Kidney drug effects, Mice, Inbred C57BL, Mice, Knockout, Monoterpenes pharmacology, Positive Regulatory Domain I-Binding Factor 1 metabolism, Positive Regulatory Domain I-Binding Factor 1 genetics, Spleen drug effects, Spleen pathology, Spleen immunology, Terpenes, Disease Models, Animal, G-Protein-Coupled Receptor Kinase 2 antagonists & inhibitors, G-Protein-Coupled Receptor Kinase 2 metabolism, Lupus Erythematosus, Systemic chemically induced, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic pathology, Plasma Cells drug effects
- 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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