Effection Of The ILC2s Differentiation Mediated By ICOSL/ICOS Signaling Pathway On Immunization Of Mice Infected With Schistosoma Japonicum

Schistosoma japonicum infection caused by cumulative liver granuloma inflammation and subsequently fibrosis is the central part of the disease.CD4⁺T cells play critical roles in both host humoral immunity and cellular immunity against parasitic infection and immunopathology in schistosomiasis.Studies have shown that ILC2s mainly mediate type II immune responses and is closely related to resist parasitic infection.However,its immune regulation mechanism is not yet clear and the relationship between ILC2s and Th2 is still unknow.The co-stimulatory signal ICOSL/ICOS plays an important role in chronic inflammation and fibrosis caused by schistosomiasis.It has been reported that the proliferation and differentiation of ILC2s is regulated by co-stimulatory signal ICOSL/ICOS,but the specific regulatory mechanism to be further clarified.In this study,We established mice ICOSL-KO,ICOSL^+/-and wild-type controls mice as animal models for schistosomiasis.To clarify ICOSL/ICOS signal pathway mediate the regulation role and key signal molecular of ILC2s differentiation and effector in the development of immunopathology in mice infected with S.japonicum.It provides a new idea and scientific basis for the mechanism of schistosomiasis immune pathology and the treatment of schistosomiasis liver fibrosis.?.The immunomodulatory effect and molecular mechanism of ILC2s in the development of immunopathology in mice infected S.japonicumObjective:to study the dynamic changes and immunomodulatory effect of ILC2s in the development of immunopathology in mice infected with S.japonicumMethods:1.Kinetic analysis of ILC2s ratio and effector cytokine IL-13 of ILC2s in lymphocytes of liver,spleen and mesenteric lymph nodes of mice analyzed by Flow cytometry on the day before infection?0 week?,and the early stages of infection?4weeks postinfection?,acute infected stage?7 weeks?,acute infected stage?9 weeks postinfection?,chronic infected stage?12 weeks postinfection?,fibrosis stage?16 weeks postinfection?.2.The spleen lymphocytes of mice were stimulated with SEA for 72 hours on the day before infection?0 week?and at 4,7,12 and 16 weeks postinfection.The concentrations of cytokines IL-13 in the culture supernatants were measured by a sandwich ELISA according to the manufacture's guideline.3.The hepatic fibrosis level in mice infected with S.japonicum was dynamically observed by Masson staining.Immunohistochemistry was used to detect the expression level of IL-13 in the liver egg granuloma in the same infected period.Results:1.The Flow cytometry analysis showed that the percentage of ILC2s in the liver,spleen and mesenteric lymph nodes of mice increased from 4 weeks after infection,further increased at 7 weekspost-infection?P<0.05 or P<0.01?,reached the peak at 12 weeks?P<0.01 or P<0.001?and decreased significantly at 16 weeks?P<0.01 or P<0.001?.2.The concentrations of cytokines IL-13 in the culture supernatants increased from4 weeks after infection,further increased at 7 weeks post-infection?P<0.001?,reached the peak at 12 weeks?P<0.01?and decreased at 16 weeks.3.The expression level of IL-13 in liver egg granuloma increased from 4 weeks after infection,peaked 12 weeks after infection and still have a higher level subsequently.Conclusion:ILC2s proliferation and the effectiveness factor IL-13 were positively correlated with eggs granulomatous inflammation and liver fibrosis.in mice infected with S.japonicum.?.The immunomodulatory effect of ILC2s and effector cytokine IL-13 of ILC2s mediated by ICOSL/ICOS signal in the development of immunopathology in mice infected S.japonicumObjective:to study the regulation function of ILC2s differentiation mediated by ICOSL/ICOS signal in the development of immunopathology in mice infected with S.japonicum.Methods:1.Kinetic analysis of ILC2s ratio and effector cytokine IL-13 of ILC2s in lymphocytes of liver,spleen andmesenteric lymph nodes from ICOSL-KO,ICOSL^+/-and wild-type control mice analyzed by Flow cytometry on the day before infection?0 week?,and the early stages of infection?4 weeks postinfection?,acute infected stage?7 weeks?,acute infected stage?9 weeks postinfection?,chronic infected stage?12 weeks postinfection?,fibrosis stage?16 weeks postinfection?.2.The spleen lymphocytes of ICOSL-KO mice were stimulated with SEA for 72hours on the day before infection?0 week?and at 4,7,12,and 16 weeks postinfection.The concentrations of cytokines IL-13 in the culture supernatants were measured by a sandwich ELISA according to the manufacture's guideline.3.The hepatic fibrosis level in ICOSL-KO mice infected with S.japonicum was dynamically observed by Masson staining.Immunohistochemistry was used to detect the expression level of IL-13 in the liver pathology in ICOSL-KO mice.Results:1.ICOSL-KO mice infected with S.japonicum was significantly lower than that of the wild-type mice?P<0.05 or P<0.01 or P<0.001?.The expression level of effect factors of IL-13 on ILC2s from ICOSL-KO mice was significantly down-regulated in the same infected period compared to wild-type mice?P<0.05 or P<0.01 or P<0.001?.2.The expression level of IL-13 in liver egg granuloma was significantly down-regulated from ICOSL^-/-mice in the same infected period compared to wild-type mice?P<0.01?.The cytokines IL-13 in the culture supernatants were down-regulated from ICOSL-KO mice compared to their wild-type control?P<0.05 or P<0.01?.Conclusion:ICOSL deficiency strongly down-regulated ILC2s differentiation and the expression of effect factors IL-13.In a word,regulating of ILC2s immune response mediated by ICOSL/ICOS signaling pathway contribute to control hepatic fibrosis of schistosomiasis.