Different Toll-Like Receptor Stimuli Have a Profound Impact on Cytokines Required to Break Tolerance and Induce Autoimmunity 英文参考文献.docVIP

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Different Toll-Like Receptor Stimuli Have a Profound Impact on Cytokines Required to Break Tolerance and Induce Autoimmunity 英文参考文献.doc

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Different Toll-Like Receptor Stimuli Have a Profound Impact on Cytokines Required to Break Tolerance and Induce Autoimmunity 英文参考文献

DifferentToll-LikeReceptorStimuliHaveaProfound ImpactonCytokinesRequiredtoBreakToleranceand InduceAutoimmunity AlbertC.C.Lin1,2,DilanDissanayake1,2,SalimDhanji1,AlishaR.Elford1,PamelaS.Ohashi1,2,3* 1CampbellFamilyInstituteforBreastCancerResearch,OntarioCancerInstitute,Toronto,Ontario,Canada,2DepartmentofImmunology,UniversityofToronto,Toronto, Ontario,Canada,3DepartmentofMedicalBiophysics,UniversityofToronto,Toronto,Ontario,Canada Abstract Althoughtoll-likereceptor(TLR)signalsarecriticalforpromotingantigenpresentingcellmaturation,itremainsunclearhow stimulation via different TLRs influence dendritic cell (DC) function and the subsequent adaptive response in vivo. Furthermore,therelationshipbetweenTLR-inducedcytokineproductionbyDCsandtheconsequencesontheinductionof afunctionalimmuneresponseisnotclear.WehaveestablishedamurinemodeltoexaminewhetherTLR3orTLR4mediated DCmaturationhasanimpactonthecytokinesrequiredtobreaktoleranceandinduceT-cell-mediatedautoimmunity.Our studydemonstratesthatIL-12isnotabsolutelyrequiredfortheinductionofaCD8T-cell-mediatedtissuespecificimmune response,butrathertherequirementforIL-12isdeterminedbythestimuliusedtomaturetheDCs.Furthermore,wefound that IFNa is a critical pathogenic component of the cytokine milieu that circumvents the requirement for IL-12 in the induction of autoimmunity. These studies illustrate how different TLR stimuli have an impact on DC function and the inductionofimmunity. Citation:LinACC,DissanayakeD,DhanjiS,ElfordAR,OhashiPS(2011)DifferentToll-LikeReceptorStimuliHaveaProfoundImpactonCytokinesRequiredto BreakToleranceandInduceAutoimmunity.PLoSONE6(9):e23940.doi:10.1371/journal.pone.0023940 Editor:PierreBoudinot,INRA,France ReceivedJune7,2011;AcceptedJuly29,2011;PublishedSeptember12,2011 Copyright:?2011Linetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: