ReviewBrainAutoimmunityandIntestinalMicrobiota:100TrillionGameChangersHartmutWekerle1,*Tcellsplayacriticalroleinautoimmunediseasesinthebrain,particularlyinmultiplesclerosis(MS).SinceTcellsarenormallypreventedfromcrossingtheblood–brainbarrier(BBB),autoimmunityrequiresprioractivationofnaturallyoccurringautoreactiveTcellsinperipheraltissue.Recently,acriticalroleforthemicrobiotainthisactivationprocesshasemerged.Here,wereviewtheroleofgut-associatedlymphoidtissues(GALT)asamajorsiteforthephenotypicchangesthatallowthemigrationofautoreactiveTcellstothebrain.Addition-ally,weexaminetheinvolvementofthemicrobiotainclinicalMSaswellasotherbraindisorderssuchasParkinson’sdisease(PD),stroke,andpsychiatricdisorders.ImmunePrivilegeversusAutoimmunityintheCentralNervousSystemAutoimmunediseasesinthebrainarelikelydrivenbyTcellsthatrecognizecerebralauto-antigens.Inmostindividuals,suchbrainautoreactiveTcellclonesresideintheimmunesystemasinnocuous‘sleepers’,butunderpathologicalconditionstheycanbeactivatedtounfoldtheirpathogenicpotential.Theactivatingeventshaveremainedobscure,althoughinteractionswithinfectiousmicrobeshavebeenevokedasplausiblemechanisms[1].Along-helddogmasaysthatthecentralnervoussystem(CNS)isexemptfromimmunesurveillance,inaccessibletoimmunecellsthatpermanentlyroamthroughtherestofthebodysearchingforpotentiallydangerousintrudersortransformedtumorcells.Theconceptofthisexceptionalstatus,knownastheimmunologicalprivilegeofthebrain,originatesfromtrans-plantationexperiments.In1921,Shiraireportedthatratsarcomacellswerepromptlyrejectedwhengraftedtoperipheralorgansofmice,butpersistedandgrewwellwhengraftedinthebrain[2].Thus,doesthismeanthatthebrain,themostcomplexorgan,lacksprotectionagainstforeign,potentiallydangerousintruders?Decadeslater,Medawarfoundawayoutoftheapparentparadox.Whileheconfirmedthesurvivalofforeignskintransplantsinthebrain,henotedthatsurvivalofthebraingraftscouldbeabruptlyterminatedbysensitizingtherecipientbytransplantingdonorskintoaperipheralsite[3].Thisconfirmedth...
