Microglia-dependent synapse loss in type I interferon-mediated lupus.[2017][Nature][10.1038nature22821]

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1、LEttERdoi:10.1038/nature22821Microglia-dependentsynapselossintypeIinterferon-mediatedlupusAllisonR.Bialas1,JessyPresumey1,AbhishekDas1,CeesE.vanderPoel1,Peterh.Lapchak2,LukaMesin3,GabrielVictora3,GeorgeC.tsokos2,ChristianMawrin4,5,Ronaldherbst6&MichaelC.Carroll1Syst

2、emiclupuserythematosus(SLE)isanincurableautoimmuneanti-IFNARantibodybehavedsimilarlytowild-typemice,indicatingdiseasecharacterizedbyautoantibodydepositionintissuessuchtheinvolvementofIFNARsignallingorperipheralautoimmunityinaskidney,skinandlungs.Notably,upto75%ofpat

3、ientswithSLEgeneral(Fig.1a–d).Notably,the564Igistrainshowednoinflammationexperienceneuropsychiatricsymptomsthatrangefromanxiety,orcellularinfiltrationinthebrain(ExtendedDataFig.2a–c),suggestingdepressionandcognitiveimpairmenttoseizuresand,inrarecases,thattreatmentwi

4、ththeanti-IFNARantibodywasprobablyaffectingpsychosis—collectivelythisisreferredtoascentralnervoussystemCNS-residentcellsratherthaninfiltratingimmunecells.(CNS)lupus1–4.Insomecases,certainautoantibodies,suchasanti-Microglia,residentmacrophagesofthebrain,respondtoloca

5、lNMDARoranti-phospholipidantibodies5,6,promoteCNSlupus.inflammationorCNSdamagebybecomingreactiveandincreasingHowever,inmostpatients,themechanismsthatunderliethesephagocyticactivityandinflammatorycytokineproduction10.Reactivesymptomsareunknown.CNSlupustypicallypresen

6、tsatlupusmicrogliahavebeendetectedinsomelupus-pronemousemodels11,12.diagnosisorwithinthefirstyear,suggestingthatearlyfactorsHowever,whetherthesecellspromoteCNSdiseaseinlupusorariseincontributingtoperipheralautoimmunitymaypromoteCNSlupusresponsetoCNSdiseaseinlupusisu

7、nclear.Todeterminewhetherandsymptoms.Herewereportbehaviouralphenotypesandsynapselosswhenreactivemicrogliadevelopin564IgiandNZB/NZWlupus-proneinlupus-pronemicethatarepreventedbyblockingtypeIinterferonstrains,bothofwhichhaveIFNAR-dependentlupuspathology8,9,13,14,(IFN)

8、signalling.Furthermore,weshowthattypeIIFNstimulatesweassessedmicroglialactivationthroughcellmorphologyandCD68microgliatobecomereactiveande