Session Type: Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: The adaptor protein, Src homology 3 domain-binding protein 2 (SH3BP2), is widely expressed in immune cells, such as myeloid cells, B cells, and T cells. It controls intracellular signaling pathways such as Syk and Src. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model and to explore differential phenotypes in immune cell sub-populations isolated from SH3BP2-deficient mice.
Methods: For the lupus model, we used Faslpr mice (C57BL/6 background). Clinical and immunological phenotypes were compared between Faslpr and SH3BP2-deficient Faslpr mice. Splenomegaly and renal involvement were assessed in 35-week-old mice. Serum levels of anti-dsDNA antibody and rheumatoid factor were determined using ELISA. Lymphocyte subsets in spleen and lymph nodes were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were generated and analyzed; differentiation of bone marrow-derived dendritic cell and activation of T cells and macrophages were determined in vitro.
Results: SH3BP2 deficiency significantly reduced lupus-like phenotypes, such as splenomegaly, renal involvement, elevated serum dsDNA antibody and rheumatoid factor, and increased splenic B220+CD4–CD8– T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells but it did not affect the functions of T cells and macrophages in vitro.
Conclusion: SH3BP2 deficiency ameliorated clinical and immunological manifestations in lupus-prone mice, possibly via targeting dendritic cells differentiation. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases.
To cite this abstract in AMA style:Mukai T, Kawahara K, Iseki M, Nagasu A, Nagasu H, Akagi T, Tsuji S, Ueki Y, Ishihara K, Kashihara N, Morita Y. SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/sh3bp2-deficiency-ameliorates-murine-systemic-lupus-erythematosus/. Accessed November 24, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/sh3bp2-deficiency-ameliorates-murine-systemic-lupus-erythematosus/