IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice

TheclearassociationofTh17�cellswithautoimmunepathogenicityimplicatesTh17�cytokinesascriticalmedi- atorsofchronicautoimmunediseasessuchasEAE.�TostudytheimpactofIL-17AonCNSinflammation,�we� generatedtransgenicmiceinwhichhighlevelsofexpressionofIL-17AcouldbeinitiatedafterCre-mediated� recombination.�AlthoughubiquitousoverexpressionofIL-17Aledtoskininflammationandgranulocytosis,� Tcell-specificIL-17Aoverexpressiondidnothaveaperceptibleimpactonthedevelopmentandhealthofthe� mice.�InthecontextofEAE,�neithertheTcell-drivenoverexpressionofIL-17Anoritscompletelosshada� majorimpactonthedevelopmentofclinicaldisease.�SinceIL-17Fmaybeabletocompensateforthelossof� IL-17A,�wealsogeneratedIL-17F-deficientmice.�ThisstrainwasfullysusceptibletoEAEanddisplayedunal- teredemergenceandexpansionofautoreactiveTcellsduringdisease.�Toeliminatepotentialcompensatory� effectsofeithercytokine,�wetreatedIL-17F-deficientmicewithantagonisticmonoclonalantibodiesspecific� forIL-17Aandfoundagainonlyaminimalbeneficialimpactondiseasedevelopment.�Weconcludetherefore� thatbothIL-17AandIL-17F,�whileprominentlyexpressedbyanencephalitogenicTcellpopulation,�mayonly� marginallycontributetothedevelopmentofautoimmuneCNSdisease.