Down‐regulation of survivin alleviates experimental arthritis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: T cells;    Blimp‐;    1;    p53;    Treg;    erosions;    synovitis;   

DOI  :  10.1189/jlb.3A0714-317R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Survivinisaproto‐oncogenethatregulatescelldivisionandapoptosis.Itisamolecularmarkerofcancer.Recently,survivinhasemergedasafeatureofRA,associatedwithseverejointdamageandpoortreatmentresponse.Thepresentstudyexaminedifinhibitionofsurvivinaffectsexperimentalarthritis,whichwasinducedinmBSA‐immunizedmicebyaninjectionofmBSAinthekneejointordevelopedspontaneouslyincollagentypeII‐immunizedmice.TheinhibitionofsurvivintranscriptionbyalentivirusshRNAconstructalleviatedjointinflammationandreducedbonedamage.Theinhibitionofsurvivinreducedthelevelsofmetalloproteinases,β‐catenin,andvimentin,limitingtheinvasivecapacityofsynovia,whilenoinhibitionofosteoclastogenesiscouldbefound.Theinhibitionofsurvivinledtoap53‐independentreductionofTcellproliferationandfavoredthetranscriptionandactivityofBlimp‐1,whichlimitedIL‐2productionandfacilitatedformationofregulatoryFoxp3+CD4+andeffectorCD8+Tcells.Thestudyshowsthattheinhibitionofsurvivinissufficienttoreducejointinflammationandbonedamageinpreclinicalmodelsofarthritis.Antiarthriticeffectsofsurvivininhibitionarerelatedtop53‐independentcontroloflymphocyteproliferation...

【 授权许可】

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