D1-like dopamine receptors promote B-cell differentiation in systemic lupus erythematosus.
B cell
D1-like receptor
Dopamine receptor
Systemic lupus erythematosus
Therapeutic target
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
17 Oct 2024
17 Oct 2024
Historique:
received:
02
08
2024
accepted:
08
10
2024
medline:
18
10
2024
pubmed:
18
10
2024
entrez:
17
10
2024
Statut:
epublish
Résumé
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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
D1-like receptors probably promote B-cell differentiation through the PTGS2/PRDM1 pathway.
Identifiants
pubmed: 39420360
doi: 10.1186/s12964-024-01885-3
pii: 10.1186/s12964-024-01885-3
doi:
Substances chimiques
Receptors, Dopamine D1
0
Cyclooxygenase 2
EC 1.14.99.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
502Subventions
Organisme : Natural Science Foundation of Hunan Province of China
ID : 2024JJ4077
Organisme : the health research project of Hunan Provincial Health Commission of China
ID : W20243055
Organisme : National Natural Science Foundation of China
ID : 82473530
Informations de copyright
© 2024. The Author(s).
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