CCL22 regulates experimental autoimmune encephalomyelitis by controlling inflammatory macrophage accumulation and effector function

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

关键词: trafficking;    migration;    CNS;    multiple sclerosis;    autoimmunity;    EAE;   

DOI  :  10.1189/jlb.0810442

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

EAEisademyelinatingdiseaseoftheCNSandservesasamousemodelofMS.ExpressionofCCL22inthedrainingLNsandspinalcordcorrelatedwiththeonsetofclinicalEAEdevelopmentandremainedelevated.Administrationofanti‐CCL22atthetimeofautoantigenimmunizationdelayedtheinitiationofclinicaldiseaseanddampenedtheseverityofpeakinitialdiseaseandrelapses.ReducedEAEseveritycorrelatedwiththereductionofpathologyandleukocytesintheCNS,particularly,activatedCD11b+Ly6Chimacrophages.TherewerenodifferencesineffectorTcell‐proliferativeresponsesoreffectorTcellIFN‐γorIL‐17responses.However,treatmentattheonsetofdiseasedidnotreducediseaseprogression.TreatmentofadoptiveTcelltransferrecipientmicewithanti‐CCL22resultedindecreasedclinicaldiseasedevelopmentaccompaniedbyadecreaseinCNSaccumulationofCD11b+Ly6Chimacrophages.NeutralizationofCCL22resultedinamacrophagepopulationwhoseeffectorcytokineexpressionconsistedofdecreasedTNFandincreasedIL‐10,aphenotypemoreconsistentwithM2macrophages.ThiswascorroboratedbyinvitroculturesofmacrophageswithCCL22.TheseresultssuggestthatCCL22functionstoregulatedevelopmentofEAEthroughmacrophagechemoattractionandeffectorfunction...

【 授权许可】

CC BY