Schistosoma Japonicum infection in Treg-specific USP21 knock-out mice

USP21, an E3 de-ubiquitin enzyme playing vital roles in physiological activities, is important for Treg cells to maintain immune homeostasis and control immune tolerance. To understand its diverse functions and potential mechanism is essential for disease development. We, using the USP21 gene-conditional knock-out mice model of Schistosoma Japonicum infection, found more cercariae developed into adults, and more eggs deposited in the liver in KO mice. However, immunohistochemistry showed the degree and the area of egg granuloma and liver fibrosis were both reduced. This suggested knock-out USP21 did affect the immunoregulation between schistosomes and the host. In KO mice the content of IFN-gamma and IL-4, and the expression of anti-SEA IgG and anti-SWAP IgG both increased in the liver, spleen and blood by flow cytometry, while the content of IL-10, lL-17A, IL-23, IL-9 and the expression of USP21 and anti-SEA IgM decreased. This indicated USP21-knockout-Tregs promoted both Th1-type and Th2-type immunity and inhibited other immunities during schistosomes infection, which disordered the host immunity. This study revealed the immunomodulatory of USP21 and preliminarily suggests it might be essential to regulate the complex immune network between the host and schistosomes. USP21 provides a new possible target for schistosomiasis treatment in the future. Author summary Schistosomiasis is a common neglected tropical disease that affects more than 230 million people worldwide. Therefore, the study on the mechanism of immune interaction between schistosomas and the host is not only helpful for the understanding of immune homeostasis, but also helpful for the further development of the treatment of schistosomiasis. Ubiquitin Specific Protease 21(USP21) has been shown to be involved in the regulation of many biological processes, such as maintaining immune homeostasis and regulating cell growth. Here, we observed that the specific deletion of USP21 led to the decrease of mice’s ability to resist schistosomes infection and promoted the survival of schistosomes. It was also proved that unstable regulatory T cells would produce polarization phenomenon and promote differentiation to helper T cells, which would lead to disorder of immune response in mice. However, this process reduced the serious immune pathological damage caused by egg granuloma. Our findings reveal that USP21 may be an important molecule regulating immune interaction between Schistosoma japonicum and the host.