Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice
AbstractSH3 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. View Full-Text
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Nagasu, A.; Mukai, T.; Iseki, M.; Kawahara, K.; Tsuji, S.; Nagasu, H.; Ueki, Y.; Ishihara, K.; Kashihara, N.; Morita, Y. Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice. Cells 2019, 8, 402.
Nagasu A, Mukai T, Iseki M, Kawahara K, Tsuji S, Nagasu H, Ueki Y, Ishihara K, Kashihara N, Morita Y. Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice. Cells. 2019; 8(5):402.Chicago/Turabian Style
Nagasu, Akiko; Mukai, Tomoyuki; Iseki, Masanori; Kawahara, Kyoko; Tsuji, Shoko; Nagasu, Hajime; Ueki, Yasuyoshi; Ishihara, Katsuhiko; Kashihara, Naoki; Morita, Yoshitaka. 2019. "Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice." Cells 8, no. 5: 402.
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