Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
How type I interferons shape myeloid cell function in CNS autoimmunity | |
关键词: MS; EAE; microglia; inflammasome; TRAIL; | |
DOI : 10.1189/jlb.0112043 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
TheprecisemechanismsunderlyingtheeffectsofIFN‐IinCNSautoimmunityremainpoorlyunderstooddespitethelong‐standinguseofthesecytokinesasfirst‐linedisease‐modifyingdrugsinthetreatmentofRRMS,achronicdemyelinatingCNSautoimmunedisease.SystemicuseofIFN‐Iresultsinpleiotropicimmunomodulationlinkingtheinnateandadaptiveimmuneresponses.RecentresearchhasdemonstratedthatinthesettingofCNSautoimmunity,IFNs‐Ihavemultipleeffectsonmyeloidcellsubsets,suchascirculatingmonocytes,granulocytes,DCs,andtissuemacrophages,suchasmicroglia.Thesediverseeffectsincludechangesincellactivation,maturation,antigenpresentation,andcytokineproduction,thusinfluencingTcelldifferentiationandexpansion,aswellastheregulationofexecutivefunctions,suchasapoptosisandphagocytosis.Moreover,currentdatasuggestthattheengagementoftheIFNARonmyeloidcellschangestheactivationstatusoftheinflammasomeinacelltype‐specificmanner.Whereasmostreportssupportprimarilyimmune‐suppressiveeffectsofIFN‐Ionmyeloidcells,endogenouslyproduced,exogenouslyinduced,andperipherallyadministeredIFNs‐IexertcomplexdifferentialspatialeffectsduringCNSautoimmuneinflammation.Clearlycharacterizingthemolecularandcellularbasisoftheseeffectspromisestoyieldviabletargetsforamoredirected,localized,celltype‐specificIFN‐I‐basedtherapeuticapproach.ThiskindofapproachwouldallowforreplacingthecurrenttreatmentstrategyinMSofbroadlyandunselectivelyalteringallimmuneresponses,regardlessoftheirbeneficialordetrimentalnature...
【 授权许可】
CC BY
【 预 览 】
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