Adaptive Autoimmunity and Foxp3-Based Immunoregulation in Zebrafish 英文参考文献.docVIP

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Adaptive Autoimmunity and Foxp3-Based Immunoregulation in Zebrafish 英文参考文献.doc

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Adaptive Autoimmunity and Foxp3-Based Immunoregulation in Zebrafish 英文参考文献

AdaptiveAutoimmunityandFoxp3-Based ImmunoregulationinZebrafish FranciscoJ.Quintana1*,AntonioH.Iglesias1,MauricioF.Farez1,MarioCaccamo2,EvanJ.Burns1 ,Nasim Kassam3,MohamedOukka3,HowardL.Weiner1* 1CenterforNeurologicDiseases,BrighamandWomen’sHospital,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica,2EMBLOutstation-Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom, 3Center for Neurologic Diseases, Brigham and Women’s Hospital,HarvardMedicalSchool,Cambridge,Massachusetts,UnitedStatesofAmerica Abstract Background:Jawedvertebratesgeneratetheirimmune-receptorrepertoirebyarecombinatorialmechanismthathasthe potentialtoproduceharmfulautoreactivelymphocytes.Inmammals,peripheraltolerancetoself-antigensisenforcedby Foxp3+regulatoryTcells.Recombinatorialmechanismsalsooperateinteleosts,butactiveimmunoregulationisthoughtto bealateincorporationtothevertebratelineage. Methods/Principal Findings: Here we report the characterization of adaptive autoimmunity and Foxp3-based immunoregulation in the zebrafish. We found that zebrafish immunization with an homogenate of zebrafish central nervous system (zCNS) triggered CNS inflammation and specific antibodies. We cloned the zebrafish ortholog for mammalian Foxp3(zFoxp3) whichinduced aregulatory phenotype on mouseT cells andcontrolled IL-17 productionin zebrafishembryos. Conclusions/Significance: Our findings demonstrate the acquisition of active mechanisms of self-tolerance early in vertebrate evolution, suggesting that active regulatory mechanisms accompany the development of the molecular potential for adaptive autoimmunity. Moreover, they identify the zebrafish as a tool to study the molecular pathways controllingadaptiveimmunity. Citation:QuintanaFJ,IglesiasAH,FarezMF,CaccamoM,BurnsEJ,etal.(2010)AdaptiveAutoimmunityandFoxp3-BasedImmunoregulationinZebrafish.PLoS ONE5(3):e9478.doi:10.1371/journal.pone.0009478 Editor:DeryaUnutmaz,NewYorkUniversity,UnitedStatesof