Expression of human gene coding RORγT receptor depends on the Sp2 transcription factor

[摘要] Th17cellsareinvolvedintheimmuneresponseagainstpathogens,autoimmunity,andtumorprogression.ThedifferentiationofhumanTh17cellsrequirestheupregulationofRORγT,whichinhumancellsisstillnotwellunderstood.Weidentified2putativebindingmotifsforspecificityproteintranscriptionfactorsfromthespecificityprotein/Kruppel‐likefactorfamilyinthepromoterofhumanRORγTandinvestigatedtheinvolvementofspecificityproteinsinthetranscriptionalregulationofthisgene.Tothisend,ahumanlymphocyticcelllineandinvitro‐differentiatedTh17cellswereusedinpromoteractivityassays,insitumutagenesis,chromatinimmunoprecipitation,andreal‐timeRT‐PCRassays.Insomeexperiments,specificityproteinexpressionandactivitywasinhibitedbysiRNAandmithramycinA.Theresultsshowedthatthetranscriptionfactorspecificityprotein2recognizedbindingmotifsinthehumanRORγTpromoter,whichwascriticalformaintainingexpression.Furthermore,specificityprotein2wasnecessaryformaximumIL‐17expressionininvitro‐differentiatedTh17cells.Theseobservationsdemonstratethesignificantroleofspecificityprotein2intheregulationoftheTh17signaturetranscriptionfactorRORγTandthemaintenanceoftheTh17phenotype.Thefindingsalsosuggestthatspecificityprotein2playsaroleinTh17‐dependentphysiologicandpathologicimmuneresponsesandmightserveasapotentialnoveltargetfortheirmodulation...

[学科分类] 生理学

[关键词] RORC;Th17;specificity protein 2;mithramycin A