| First Author | Zeng S | Year | 2022 |
| Journal | Int Immunopharmacol | Volume | 103 |
| Pages | 108498 | PubMed ID | 34972067 |
| Mgi Jnum | J:319877 | Mgi Id | MGI:6865476 |
| Doi | 10.1016/j.intimp.2021.108498 | Citation | Zeng S, et al. (2022) The suppression of Brd4 inhibits peripheral plasma cell differentiation and exhibits therapeutic potential for systemic lupus erythematosus. Int Immunopharmacol 103:108498 |
| abstractText | The mechanisms that control B cell terminal differentiation remain undefined. Here, we investigate the role of bromodomain-containing protein 4 (Brd4) in regulating B cell differentiation and its therapeutic potential for B cell-mediated autoimmune diseases including systemic lupus erythematosus (SLE). We showed that Brd4 inhibitor PFI-1 suppressed plasmablast-mediated plasma cell differentiation in healthy human CD19(+) B cells. PFI-1 reduced IgG and IgM secretion in costimulation-induced human B cells. We also observed a reduced percentage of plasma cells in mice with B cell-specific deletion of the Brd4 gene (Brd4(flox/flox)CD19-cre(+)). Mechanistically, using the luciferase reporter assay and the chromatin immunoprecipitation, we explored that Brd4 regulates the expression of B lymphocyte-induced maturation protein 1 (BLIMP1), an important transcript factor that is involved in modulation of plasma cell differentiation. Interestingly, PFI-1 decreased the percentages of plasmablasts and plasma cells from patients with SLE. PFI-1 administration reduced the percentages of plasma cells, hypergammaglobulinemia, and attenuated nephritis in MRL/lpr lupus mice. Pristane-injected Brd4(flox/flox)CD19-cre(+) mice exhibited improved nephritis and reduced percentages of plasma cells. These findings suggest an essential factor of Brd4 in regulating plasma cell differentiation. Brd4 inhibition may be a potential strategy for the treatment of B cell-associated autoimmune disorders. |
