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

Autor: Xiang Z; Department of Laboratory Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Wu F; Department of Clinical Laboratory, The Affiliated Cancer Hospital of Xiangya, Central South University, Hunan Cancer Hospital, Changsha, Hunan, China., He Z; Department of Plastic Surgery, Zhongshan City People's Hospital, Zhongshan, Guangdong, China., Tan F; Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Central South University, Changsha, Hunan, China., Hu H; Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Central South University, Changsha, Hunan, China., Zou C; Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Central South University, Changsha, Hunan, China., Yi P; Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China., Liu W; Department of Laboratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China. wenenliu@163.com., Yang M; Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Central South University, Changsha, Hunan, China. yangming_0216@csu.edu.cn.
Jazyk: angličtina
Zdroj: Cell communication and signaling : CCS [Cell Commun Signal] 2024 Oct 17; Vol. 22 (1), pp. 502. Date of Electronic Publication: 2024 Oct 17.
DOI: 10.1186/s12964-024-01885-3
Abstrakt: Background: 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.
Methods: 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.
Results: 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.
Conclusion: D1-like receptors probably promote B-cell differentiation through the PTGS2/PRDM1 pathway.
(© 2024. The Author(s).)
Databáze: MEDLINE
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