Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice

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  • Akiko Nagasu
    Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
  • Tomoyuki Mukai
    Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
  • Masanori Iseki
    Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
  • Kyoko Kawahara
    Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
  • Shoko Tsuji
    Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
  • Hajime Nagasu
    Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
  • Yasuyoshi Ueki
    Indiana Center for Musculoskeletal Health, Indiana University, Bloomington, IN 46202, USA
  • Katsuhiko Ishihara
    Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
  • Naoki Kashihara
    Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
  • Yoshitaka Morita
    Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
  • Biomedical Sciences and Comprehensive Care, School of Dentistry

書誌事項

公開日
2019-04-30
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by/4.0/
DOI
  • 10.3390/cells8050402
公開者
MDPI AG

説明

<jats:p>SH3 domain-binding protein 2 (SH3BP2) is an adaptor protein that is predominantly expressed in immune cells, and it regulates intracellular signaling. We had previously reported that a gain-of-function mutation in SH3BP2 exacerbates inflammation and bone loss in murine arthritis models. Here, we explored the involvement of SH3BP2 in a lupus model. Sh3bp2 gain-of-function (P416R knock-in; Sh3bp2KI/+) mice and lupus-prone B6.MRL-Faslpr mice were crossed to yield double-mutant (Sh3bp2KI/+Faslpr/lpr) mice. We monitored survival rates and proteinuria up to 48 weeks of age and assessed renal damage and serum anti-double-stranded DNA antibody levels. Additionally, we analyzed B and T cell subsets in lymphoid tissues by flow cytometry and determined the expression of apoptosis-related molecules in lymph nodes. Sh3bp2 gain-of-function mutation alleviated the poor survival rate, proteinuria, and glomerulosclerosis and significantly reduced serum anti-dsDNA antibody levels in Sh3bp2KI/+Faslpr/lpr mice. Additionally, B220+CD4−CD8− T cell population in lymph nodes was decreased in Sh3bp2KI/+Faslpr/lpr mice, which is possibly associated with the observed increase in cleaved caspase-3 and tumor necrosis factor levels. Sh3bp2 gain-of-function mutation ameliorated clinical and immunological phenotypes in lupus-prone mice. Our findings offer better insight into the unique immunopathological roles of SH3BP2 in autoimmune diseases.</jats:p>

収録刊行物

  • Cells

    Cells 8 (5), 402-, 2019-04-30

    MDPI AG

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