How type I interferons shape myeloid cell function in CNS autoimmunity

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

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