VIP boosts regulatory T cell induction by trophoblast cells in an in vitro model of trophoblast–maternal leukocyte interaction

[摘要] InducibleregulatoryTcells(Tregs)exertatimelyandefficientimmunosuppressiveactionatthecriticalperi‐implantationstageessentialformaternaltolerancetotheconceptus.Vasoactiveintestinalpeptide(VIP)promotesanti‐inflammatoryandtolerogenicprofilesthroughbindingtoVIPreceptorsonimmunecells.WeevaluatedwhetherVIPproducedbytrophoblastcellsinducesTregsduringtheearlyinteractionofmaternalleukocyteswithtrophoblastcells,thuscontributingtomaternaltolerance.Weusedaninvitromodelofmaternalleukocyte–trophoblastcellinteractionrepresentedbycoculturesoffertilewomen'sPBMCswithahumantrophoblastcellline(Swan‐71)andevaluatedtheeffectofVIPaddedexogenouslyandoftheendogenouspolypeptide.VIPincreasedthefrequencyofCD4+CD25+FoxP3+cellsaftercoculture,andthesecellswereabletosuppressthematernalalloresponse.VIPalsoincreasedthefrequencyofCD4+IL10+andCD4+TGFβ+cells,butitdidnotmodulateIFN‐γorIL‐17production.Swan‐71secretedVIP,andtheircoculturewithmaternalPBMCssignificantlyincreasedthefrequencyofTregs.ThiseffectwasevenmorepronouncedifthetrophoblastcellshadbeenpretreatedwithVIP.Inbothsituations,theVIPantagonistpreventedtheincreaseinthefrequencyofCD4+Foxp3+cells,reflectingaspecificeffectofthepolypeptideaftertheinteractionwithSwan‐71cells.Finally,theincreaseinCD4+CD25+FoxP3+frequencywaspreventedbyananti–TGF‐βAbandaVIPantagonist.TheseresultssuggestthatVIPcouldhaveanactiveroleintheimmunoregulatoryprocessesoperatinginthematernal–placentalinterfacebycontributingtotheinductionofTregsthroughamechanisminvolvingTGF‐β1...

[学科分类] 生理学

[关键词] early pregnancy;tolerance;TGF‐βiTreg