The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with Schistosoma japonicum, we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21^fl/flFOXP3^Cre (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21^fl/flFOXP3^Cre mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between Schistosoma and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis.

中文翻译：

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Treg 特异性 USP21 敲除小鼠中的日本血吸虫感染

E3 去泛素化酶泛素特异性蛋白水解酶 21 (USP21) 在生理活动中起着至关重要的作用，并且是 Treg 细胞介导的免疫耐受所必需的。使用感染了日本血吸虫的小鼠模型，我们观察到有更多尾蚴发育成成人，更多的卵沉积在 USP21 ^fl/fl FOXP3 ^Cre (KO) 小鼠的肝脏中。然而，免疫组化显示鸡蛋肉芽肿形成和肝纤维化程度降低。在 USP21 ^fl/fl FOXP3 ^Cre小鼠体内 IFN-γ、IL-4、抗可溶性卵抗原 (SEA) IgG 和抗可溶性蠕虫抗原制剂 (SWAP) IgG 在血液中的水平增加，如使用 ELISA 和多重荧光微球免疫测定法测定的，而IL-10、IL-17A、IL-23、IL-9 和抗 SEA IgM 降低。此外，KO小鼠肝脏和脾脏中USP21蛋白和mRNA的水平降低。我们进一步观察到由 Tregs（调节性 T 细胞）放大的 Th1 反应增加，并减弱了 Th17 反应，这减轻了肝脏免疫病理学。我们推测这些变化与 Th1 样 Treg 的极化有关。我们的结果揭示了 USP21 在 Treg 细胞介导的血吸虫免疫相互作用调节中的作用和它的主人。USP21 可能具有调节血吸虫病患者肝纤维化的潜力。