Antibodies to MHC Class II Molecules Induce Autoimmunity Critical Role for Macrophages in the Immunopathogenesis of Obliterative Airway Disease 英文参考文献.docVIP

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Antibodies to MHC Class II Molecules Induce Autoimmunity Critical Role for Macrophages in the Immunopathogenesis of Obliterative Airway Disease 英文参考文献.doc

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Antibodies to MHC Class II Molecules Induce Autoimmunity Critical Role for Macrophages in the Immunopathogenesis of Obliterative Airway Disease 英文参考文献

AntibodiestoMHCClassIIMoleculesInduce Autoimmunity:CriticalRoleforMacrophagesinthe ImmunopathogenesisofObliterativeAirwayDisease MasashiTakenaka1.,VenkataswarupTiriveedhi1.,VijaySubramanian1,KiyotakaHoshinaga3, AlexanderG.Patterson1,ThalachallourMohanakumar1,2* 1Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America, 2Department of Pathology and Immunology, WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,3DepartmentofUrology,FujitaHealthUniversitySchoolofMedicine,Toyoake, Aichi,Japan Abstract Previousstudieshaveshownthatintrabronchialadministrationofantibodies(Abs)toMHCclassIresultedindevelopment ofobliterativeairwaydisease(OAD),acorrelateofchronichumanlungallograftrejection.SincedevelopmentofAbsspecific tomismatcheddonorHLAclassIIhavealsobeenassociatedwithchronichumanlungallograftrejection,weanalyzedthe role of Abs to MHC class II in inducing OAD. Administration of MHC class II Abs (M5/114) to C57BL/6 mice induced the classicalfeaturesofOADeventhoughMHCclassIIexpressionisabsentdenovoonmurinelungepithelialandendothelial cells. The induction of OAD was accompanied by enhanced cellular and humoral immune responses to self-antigens (Collagen V and K- a1Tubulin). Further, lung-infiltrating macrophages demonstrated a switch in their phenotype predominance from MW1 (F4/80+CD11c+) to MW2 (F4/80+CD206+) following administration of Abs and prior to development of OAD. Passive administration of macrophages harvested from animals with OAD but not from na?¨ve animals induced OAD lesions. We conclude that MHC class II Abs induces a phenotype switch of lung infiltrating macrophagesfromMW1(F4/80+CD11c+)toMW2(F4/80+CD206+)resultinginthebreakdownofself-tolerancealongwithan increaseinautoimmuneTh17responseleadingtoOAD. Citation:TakenakaM,TiriveedhiV,SubramanianV,HoshinagaK,PattersonAG,etal.(2012)AntibodiestoMHCClassIIMoleculesInduceAutoimmunity:Critical RoleforMacrophagesintheImmunopathogenesiso