Pathway of Toll-Like Receptor 7B Cell Activating FactorB Cell Activating Factor Receptor Plays a Role in Immune Thrombocytopenia In Vivo 英文参考文献.docVIP

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Pathway of Toll-Like Receptor 7B Cell Activating FactorB Cell Activating Factor Receptor Plays a Role in Immune Thrombocytopenia In Vivo 英文参考文献.doc

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Pathway of Toll-Like Receptor 7B Cell Activating FactorB Cell Activating Factor Receptor Plays a Role in Immune Thrombocytopenia In Vivo 英文参考文献

PathwayofToll-LikeReceptor7/BCellActivatingFactor/ BCellActivatingFactorReceptorPlaysaRoleinImmune ThrombocytopeniaInVivo QingYang1,2,3.,ShuqianXu2.,XiaofangLi4,BoWang3,5,XupingWang3,DaoxinMa2,LeiYang2, JunPeng2,MingHou2* 1DepartmentofParasitology,ShandongUniversitySchoolofMedicine,Jinan,China,2HaematologyOncologyCentre,QiluHospital,ShandongUniversity,Jinan,China, 3KeyLaboratoryofCardiovascularRemodelingandFunctionResearch,ChineseMinistryofEducationandChineseMinistryofPublicHealth,QiluHospital,Shandong University,Jinan,China,4HematologyDepartment,NanfangHospital,SouthernMedicalUniversity,Guangzhou,China,5DepartmentofTraditionalChineseMedicine, QiluHospital,ShandongUniversity,Jinan,China Abstract Immunethrombocytopenia(ITP)isanautoimmunedisordercharacterizedbyanti-plateletautoantibody-mediatedplatelet destruction.Antigen-presentingcell(APC)dysfunctionisconsideredtoplaycrucialrolesinITP.However,howAPCaffects autoreactive B cells in ITP is still unknown. Using a mouse model of immune thrombocytopenia, we demonstrated an increaseinlevelsofTLR7insplenicmononuclearcells(SMCs).UsingbothTLR7agonistandTLR7silencinglentivirus,we found stimulation of TLR7 decreased platelet counts and increased levels of platelet-associated IgG (PAIgG) in ITP mice, whichcorrelatesTLR7withplateletdestructionbyautoantibodies.LevelsofserumBAFFincreasedsignificantlyinITPmice and stimulation of TLR7 promoted secretion of BAFF. Among the three BAFF receptors, only BAFF receptor (BAFF-R) increasedinITPmice.However,activationofTLR7showednoeffectontheexpressionofBAFFreceptors.Thesefindings indicate that upregulation of TLR7 may augment BAFF secretion by APC and through ligation of BAFF-R promote autoreactiveBcellsurvivalandthusanti-plateletautoantibodyproduction.ThepathwayofTLR7/BAFF/BAFF-Rprovidesus withanexplanationofhowactivationofAPCaffectsautoantibodyproductionbyBcellsinITPandthusmightprovidea reasonabletherapeuticstrategyforITP. Citation:YangQ,XuS,LiX,WangB,WangX,etal.(2011)PathwayofToll-LikeRe