巨噬细胞增强表达诱骗受体il-13rα2及其在血吸虫病免疫病理调节中作用-macrophage enhances expression of decoy receptor il - 13rα 2 and its role in immune and pathological regulation of schistosomiasis.docxVIP

AnenhancedexpressionofthedecoyreceptorIL-13Rα2inmacrophagesanditseffectsonimmunopathogenesisofSchistosomiasisjaponicumPH.Dcandidate:WANGWeiSupervisor:JIANGZuo-junandSHENJi-longDepartmentofEpidemiologyandBiostatistics,SchoolofPublicHealthDepartmentofMicrobiologyandParasitology,AnhuiMedicalUniversity,Hefei230032ABSTRACTInterleukin(IL)-13andIL-13receptor(R)α2appeartoplayamajorroleintissuefibrosisofschistosomiasisandasthma.IL-13isproducedbyThelper2(Th2)cells.ThetwobindingreceptorchainsforIL-13includeIL-13Rα1andIL-13Rα2.Whenexpressedalone,IL-13Rα1bindsIL-13withlowaffinity.However,whenIL-13Rα1iscoexpressedwithIL-4Rα,ahigh-affinityheterodimerizedreceptorisformed,regulatingthebiologicalactivityofIL-13.Incontrast,IL-13Rα2,anessentialcomponentforbindingandinternalizationofIL-13butnotforIL-13-inducedsignaltransduction,bindsIL-13withhighaffinityandisknownasthedecoyreceptor.IL-13Rα2orsIL-13Rα2-FcfusionproteinishighlyinhibitionofIL-13activity.TotargetIL-13receptor-positivetumorcells,arecombinantfusionIL-13cytotoxintermedIL-13-PE38QQRorIL-13-PEwasdeveloped.IthasbeenshownthatIL-13cytotoxininducesapoptoticcelldeathintumorcells.IL-13Rα2chainistargetedwithareceptor-directedcytotoxinofIL-13-PEtoinducespecifickillingincancercells.Basedontheseexperimentalresults,clinicaltrialsofIL-13Rα2cancertherapyhavebeeninitiated.IL-13isakeyregulatoroftheextracellularmatrix.Itstimulatescollagenproductioninfibroblasts.Itseffectsonfibrosisaredirectwithnoeffectongranulomasize.Elucidatingthemechanismsleadingtopathologyandfibrosismayleadtomoreeffectivestrategiesforimmunologicalinterventioninavarietyofchronicdiseases.BiologicalactivityandregulationofproductionandfunctionofIL-13havebecomeanintensiveareaofresearch.IL-13alsoplaysanimportantroleinschistosomiasispathogenesis.SerumlevelsofIL-13Rα2inbothhumanandmicewereupregulatedinSchistosomamansoni(S.mansoni).IL-13Rα2-deficientmice(IL-13Rα2-/-)hadamarkedexacerbationinhepaticfibrosis.PathologywaspreventedwhenIL-13Rα2-deficientmiceweretreatedwithasolubleIL-13Rα2-F