D1-like dopamine receptors promote B-cell differentiation in systemic lupus erythematosus

• Published in: Cell communication and signaling 2024-10, Vol.22 (1), p.502-13, Article 502
• Main Authors: Xiang, Zhongyuan, Wu, Fengxi, He, Zhenghao, Tan, Fen, Hu, Haoran, Zou, Chun, Yi, Ping, Liu, Wenen, Yang, Ming
• Format: Article
• Language: English
• Subjects: Adult; Animals; B cell; B cells; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cell Differentiation; Cellular signal transduction; Complications and side effects; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; D1-like receptor; Dopamine receptor; Dopamine receptors; Female; Health aspects; Humans; Immunological research; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lupus Erythematosus, Systemic - pathology; Male; Mice; Mice, Inbred C57BL; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D1 - metabolism; Systemic lupus erythematosus; Therapeutic target
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-024-01885-3

Systemic lupus erythematosus (SLE) is an autoimmune disease that currently cannot be completely cured with a great health burden. Since the production of autoantibodies plays a key role in the pathogenesis of SLE, discovering the underlying immunoregulation mechanism of B cells will be helpful for developing promising immunotherapy for SLE. In recent studies, dopamine receptors (DRDs), G protein-coupled receptors that include D1-like and D2-like subtypes, are expressed on B cells and participate in various physiological processes, involving immune responses. However, the regulatory effect of DRDs on B cells has not been determined. This study explored the expression of DRDs on B-cell subsets from SLE patients and healthy individuals. The effects of D1-like receptor on B-cell activation and differentiation were further explored using D1-like receptor agonists or antagonists. RNA-seq and bioinformatics analyses were used to identify specific molecular mechanisms involved. The D1-like DRDs on B cells of SLE patients were highly expressed compared with those of healthy controls (HCs). D1-like receptor agonist treatment exacerbated lupus-like symptoms in pristane-induced lupus-like mice, while D1-like receptor antagonists alleviated the lupus-like phenotypes. Inhibition of D1-like receptor signals impeded B-cell differentiation, while activation of D1-like receptor signals could promote B cell differentiation. Further RNA-seq confirmed that PTGS2, a gene related to B-cell differentiation, was up-regulated once the D1-like receptor signals were activated, while BMP6 and IL-24 were up-regulated once the D1-like receptor signals were inhibited. D1-like receptors probably promote B-cell differentiation through the PTGS2/PRDM1 pathway.