SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus
dc.contributor.author | Kawahara, Kyoko | |
dc.contributor.author | Mukai, Tomoyuki | |
dc.contributor.author | Iseki, Masanori | |
dc.contributor.author | Nagasu, Akiko | |
dc.contributor.author | Nagasu, Hajime | |
dc.contributor.author | Akagi, Takahiko | |
dc.contributor.author | Tsuji, Shoko | |
dc.contributor.author | Hiramatsu-Asano, Sumie | |
dc.contributor.author | Ueki, Yasuyoshi | |
dc.contributor.author | Ishihara, Katsuhiko | |
dc.contributor.author | Kashihara, Naoki | |
dc.contributor.author | Morita, Yoshitaka | |
dc.contributor.department | Medicine, School of Medicine | en_US |
dc.date.accessioned | 2022-08-16T13:58:50Z | |
dc.date.available | 2022-08-16T13:58:50Z | |
dc.date.issued | 2021-04-17 | |
dc.description.abstract | 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 Faslpr/lpr mice. Clinical and immunological phenotypes were compared between Faslpr/lpr and SH3BP2-deficient Faslpr/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. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Kawahara K, Mukai T, Iseki M, et al. SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus. Int J Mol Sci. 2021;22(8):4169. Published 2021 Apr 17. doi:10.3390/ijms22084169 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/29776 | |
dc.language.iso | en_US | en_US |
dc.publisher | MDPI | en_US |
dc.relation.isversionof | 10.3390/ijms22084169 | en_US |
dc.relation.journal | International Journal of Molecular Sciences | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.source | PMC | en_US |
dc.subject | Src homology 3 domain-binding protein 2 | en_US |
dc.subject | Systemic lupus erythematosus | en_US |
dc.subject | Lupus mouse model | en_US |
dc.subject | Dendritic cells | en_US |
dc.title | SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus | en_US |
dc.type | Article | en_US |