Kawahara, KyokoMukai, TomoyukiIseki, MasanoriNagasu, AkikoNagasu, HajimeAkagi, TakahikoTsuji, ShokoHiramatsu-Asano, SumieUeki, YasuyoshiIshihara, KatsuhikoKashihara, NaokiMorita, Yoshitaka2022-08-162022-08-162021-04-17Kawahara 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/ijms22084169https://hdl.handle.net/1805/29776Background: 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-USAttribution 4.0 InternationalSrc homology 3 domain-binding protein 2Systemic lupus erythematosusLupus mouse modelDendritic cellsArticle