title: Blimp-1 siRNA inhibits B cell differentiation and prevents the development of lupus in mice.
abstract: Cumulative evidence suggest that B-lymphocytes play a role in the development of systemic lupus erythematosus (SLE). Thus, the therapeutic approach targeting specific B cells provides a promising way to treat SLE. Blimp-1 (B lymphocyte induced maturation protein), a transcriptional factor, controls the terminal differentiation of mature B cells to plasma cells. To explore the potential of Blimp-1 in the SLE development, we constructed the adenovirus encoding Blimp-1 siRNA, and injected it into BWF1 lupus mice. The results demonstrated that Blimp-1 siRNA decreased the Blimp-1 expression of B cells by regulating XBP-1 (X Box binding protein-1), BCMA (B-cell maturation antigen) expression through c-myc pathway. In addition, Blimp-1 siRNA eliminated anti-dsDNA antibody-producing plsma cells, reduced serum anti-dsDNA antibody levels and impeded the development of lupus. Therefore, our data provide the insight into the mechanism of Blimp-1 in SLE development and might represent a promising therapeutic strategy for autoantibody-mediated diseases.
authors.affiliation: Department of Nephrology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Zhongqi
authors.initials: Z
authors.lastname: Zhou
authors.forename: Aiju
authors.initials: A
authors.lastname: Li
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Pei
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.forename: Guangyi
authors.initials: G
authors.lastname: Liu
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Ren
authors.forename: Zhao
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D016271:Proto-Oncogene Proteins c-myc / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000071717:X-Box Binding Protein 1
chemical_list: D000974:Antibodies, Antinuclear; D053301:B-Cell Maturation Antigen; D004268:DNA-Binding Proteins; C489428:Myc protein, mouse; C513258:Prdm1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D000071701:Regulatory Factor X Transcription Factors; C490176:Tnfrsf17 protein, mouse; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D000074462:Positive Regulatory Domain I-Binding Factor 1