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雷帕霉素对TGF-β1诱导的人Treg细胞的体外影响.docx

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雷帕霉素对TGF-β1诱导的人Treg细胞的体外影响 Introduction: TRegulatory(Treg)cellsareaspecializedsubsetofTcellsthatareconstitutivelyexpressedinthebodyandcrucialinmaintainingimmunetoleranceandpreventingautoimmunediseases.Tregcellsplayanessentialroleinsuppressingtheimmuneresponseandpreventingautoimmunediseases.TheTGF-β1cytokine,amemberofthetransforminggrowthfactorfamily,isacriticalregulatorofTregcelldifferentiationandfunction.TGF-β1signalingpromotesthedifferentiationandactivationofTregcells,aidingintheimmunesystem'sabilitytomaintainimmunetolerance.Inrecentyears,researchershavebeenexploringthepotentialofdrugslikerapamycintoimproveTregcellfunctionandreducetheseverityofautoimmunediseases.TheaimofthispaperistoreviewtheliteratureregardingtheinvitroimpactofrapamycinonTGF-β1-inducedTregcells. Rapamycin: RapamycinisamacrolideantibioticthatbindstoFKBP12,anintracellularprotein.ThecomplexformedbyrapamycinandFKBP12inhibitsthephosphorylationofribosomalproteinS6kinase1(S6K1),causingselectiveinhibitionofthemammaliantargetofrapamycin(mTOR)complex1(mTORC1)signalingpathway.Asaresult,rapamycinsignificantlymodulatesTcelldifferentiation,proliferation,andactivity,leadingtothesuppressionofimmuneresponses. ImpactofRapamycinonTGF-β1-inducedTregcells: ThecurrentunderstandingofthemodulationofTGF-β1-inducedTregcellsbyrapamycincomesfromcellcultureexperimentsandpreclinicalstudies.SeveralstudieshavereportedthebeneficialeffectsofrapamycinonTregcells,includingpromotionofTregcelldifferentiation,suppressionofTh17celldifferentiation,andinhibitionofeffectorTcellandBcellfunction.Invitro,rapamycinhasbeenshowntoincreasethefrequencyofCD4+CD25+Foxp3+Tregcellsinbothmouseandhumancells. TGF-β1signalingthroughSMADtranscriptionfactorsplaysavitalroleinTregcelldifferentiation.TGF-β1-inducedTregcellsexhibitenhancedFoxp3expression,suppressivefunction,andstabilitycomparedtoTregcellsinducedbyothercytokines.Invitro,rapamycinhasbeenshowntoenhanceTregcelldifferentiationandfunctioninthepresenceofTGF-β1.Moreover,rapamycinpromotesthesuppressive