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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: early pregnancy;    tolerance;    TGF‐;    β;    iTreg;   

DOI  :  10.1189/jlb.1A1014-492RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 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...

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