Excess Circulating Alternatively Activated Myeloid (M2) Cells Accelerate ALS Progression While Inhibiting Experimental Autoimmune Encephalomyelitis 英文参考文献.docVIP
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Excess Circulating Alternatively Activated Myeloid (M2) Cells Accelerate ALS Progression While Inhibiting Experimental Autoimmune Encephalomyelitis 英文参考文献
ExcessCirculatingAlternativelyActivatedMyeloid(M2)
CellsAccelerateALSProgressionWhileInhibiting
ExperimentalAutoimmuneEncephalomyelitis
IlanVaknin1.,GiladKunis1.,OmerMiller1,OlegButovsky1,ShayBukshpan1,DavidR.Beers2,
JennyS.Henkel2,EtiYoles3,StanleyH.Appel2*,MichalSchwartz1*
1DepartmentofNeurobiology,TheWeizmannInstituteofScience,Rehovot,Israel,2DepartmentofNeurology,MethodistNeurologicalInstitute,TheMethodistHospital
ResearchInstitute,TheMethodistHospital,Houston,Texas,UnitedStatesofAmerica,3NeuroQuestLtd.MisgavVentureAccelerator,MisgavBusinessPark,Misgav,Israel
Abstract
Background:CirculatingimmunecellsincludingautoreactiveTcellsandmonocyteshavebeendocumentedaskeyplayers
inmaintaining,protectingandrepairingthecentralnervoussystem(CNS)inhealthanddisease.Here,wehypothesizedthat
neurodegenerativediseasesmightbeassociated,similarlytotumors,withincreasedlevelsofcirculatingperipheralmyeloid
derivedsuppressorcells(MDSCs),representingasubsetofsuppressorcellsthatoftenexpandunderpathologicalconditions
andinhibitpossiblerecruitmentofhelperTcellsneededforfightingoffthedisease.
Methods and Findings: We tested this working hypothesis in amyotrophic lateral sclerosis (ALS) and its mouse model,
which are characterized by a rapid progression once clinical symptoms are evident. Adaptive transfer of alternatively
activated myeloid (M2) cells, which homed to the spleen and exhibited immune suppressive activity in G93A mutant
superoxidedismutase-1(mSOD1)miceatastagebeforeemergenceofdiseasesymptoms,resultedinearlierappearanceof
diseasesymptomsandshorterlifeexpectancy.Thesameprotocolmitigatedtheinflammation-induceddiseasemodelof
multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), which requires circulating T cells for disease
induction. Analysis of whole peripheral blood samples obtained from 28 patients suffering from sporadic ALS (sALS),
+
revealedatwo-foldincreaseinthepercentageofcirculatingMDSCs(LIN2/LowHLA-DR2CD33 )comparedtocontrols.
Conclusions: Taken toge
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