| First Author | Kawahara K | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 8 | PubMed ID | 33920631 |
| Mgi Jnum | J:325760 | Mgi Id | MGI:6718082 |
| Doi | 10.3390/ijms22084169 | Citation | Kawahara K, et al. (2021) SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus. Int J Mol Sci 22(8) |
| abstractText | BACKGROUND: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells. It controls intracellular signaling pathways. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model. METHODS: For the lupus model, we used Fas(lpr/lpr) mice. Clinical and immunological phenotypes were compared between Fas(lpr/lpr) and SH3BP2-deficient Fas(lpr/lpr) mice. Splenomegaly and renal involvement were assessed. Lymphocyte subsets in the spleen were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were analyzed; T cells and bone marrow-derived dendritic cells and macrophages were analyzed in vitro. RESULTS: SH3BP2 deficiency significantly reduced lupus-like phenotypes, presented as splenomegaly, renal involvement, elevated serum anti-dsDNA antibody, and increased splenic B220(+)CD4(-)CD8(-) T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Furthermore, SH3BP2 deficiency did not substantially affect the characteristics of T cells and macrophages in vitro. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells in vitro and reduced the number of dendritic cells in the spleen of the lupus-prone mice. CONCLUSIONS: SH3BP2 deficiency ameliorated lupus-like manifestations. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases. |
