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Biliary Innate Immunity Function and Modulation英文文献资料.doc

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Biliary Innate Immunity Function and Modulation英文文献资料

HindawiPublishingCorporation MediatorsofIn?ammation Volume2010,ArticleID373878,9pages doi:10.1155/2010/373878 ReviewArticle BiliaryInnateImmunity:FunctionandModulation KenichiHaradaandYasuniNakanuma DepartmentofHumanPathology,KanazawaUniversityGraduateSchoolofMedicine,Kanazawa920-8640,Japan CorrespondenceshouldbeaddressedtoKenichiHarada,kenichih@med.kanazawa-u.ac.jp Received3December2009;Accepted22June2010 AcademicEditor:AndrewParker Copyright?2010K.HaradaandY.Nakanuma. This is an open access article distributed under the Creative Commons AttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkis properlycited. Biliary innate immunity is involved in the pathogenesis of cholangiopathies in patients with primary biliary cirrhosis (PBC) and biliary atresia. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR) family andrecognizepathogen-associatedmolecularpatterns(PAMPs).TolerancetobacterialPAMPssuchaslipopolysaccharidesisalso importanttomaintainhomeostasisinthebiliarytree,buttolerancetodouble-strandedRNA(dsRNA)isnotfound.InPBC,CD4- positiveTh17cellscharacterizedbythesecretionofIL-17areimplicatedinthechronicin?ammationofbileductsandthepresence ofTh17cellsaroundbileductsiscausallyassociatedwiththebiliaryinnateimmuneresponsestoPAMPs.Moreover,anegative regulatorofintracellularTLRsignaling,peroxisomeproliferator-activatedreceptor-γ(PPARγ),isinvolvedinthepathogenesisof cholangitis.ImmunosuppressionusingPPARγligandsmayhelptoattenuatethebileductdamageinPBCpatients.Inbiliaryatresia characterizedbyaprogressive,in?ammatory,andsclerosingcholangiopathy,dsRNAvirusesarespeculatedtobeanetiological agentandtodirectlyinduceenhancedbiliaryapoptosisviatheexpressionoftumornecrosisfactor-relatedapoptosis-inducing ligand(TRAIL).Moreover,theepithelial-mesenchymaltransition(EMT)ofbiliaryepithelialcellsisalsoevokedbythebiliary innateimmuneresponsetodsRNA. 1.Introduction Humanbileissterileu