662|NATURE|VOL546|29JUNE2017LETTERdoi:10.1038/nature22795HumanfetaldendriticcellspromoteprenatalT-cellimmunesuppressionthrougharginase-2NaomiMcGovern1,AmandaShin1,2,GillianLow1,DonovanLow1,KaiboDuan1,LeongJingYao3,RashaMsallam1,IvyLow1,NurhidayaBinteShadan1,HermiRSumatoh1,ErinSoon1,JosephineLum1,EstherMok1,SandraHubert1,PeterSee1,EdwinHuangKunxiang4,YieHouLee5,6,BaptisteJanela1,MaheshChoolani7,8,CitraNurfarahZainiMattar7,8,YipingFan4,8,TonyKiatHonLim9,DedrickKokHongChan10,Ker-KanTan10,11,JohnKitChungTam11,ChristopherSchuster12,AdelheidElbe-Bürger12,Xiao-nongWang13,VenetiaBigley13,MatthewCollin13,MuzlifahHaniffa13,AndreasSchlitzer1,14,15,MichaelPoidinger1,SalvatoreAlbani3,AnisLarbi1,EvanWNewell1,JerryKokYenChan1,4,8,16*&FlorentGinhoux1*Duringgestationthedevelopinghumanfetusisexposedtoadiverserangeofpotentiallyimmune-stimulatorymoleculesincludingsemi-allogeneicantigensfrommaternalcells1,2,substancesfromingestedamnioticfluid3,4,foodantigens5,andmicrobes6.Yetthecapacityofthefetalimmunesystem,includingantigen-presentingcells,todetectandrespondtosuchstimuliremainsunclear.Inparticular,dendriticcells,whicharecrucialforeffectiveimmunityandtolerance,remainpoorlycharacterizedinthedevelopingfetus.Hereweshowthatsubsetsofantigen-presentingcellscanbeidentifiedinfetaltissuesandarerelatedtoadultpopulationsofantigen-presentingcells.Similartoadultdendriticcells,fetaldendriticcellsmigratetolymphnodesandrespondtotoll-likereceptorligation;however,theydiffermarkedlyintheirresponsetoallogeneicantigens,stronglypromotingregulatoryT-cellinductionandinhibitingT-celltumour-necrosisfactor-αproductionthrougharginase-2activity.Ourresultsrevealapreviouslyunappreciatedroleofdendriticcellswithinthedevelopingfetusandindicatethattheymediatehomeostaticimmune-suppressiveresponsesduringgestation.Weusedacombinationofflowcytometryandgenearrayanalysistocharacterizehumanfetalantigen-presentingcells(APC)andcomparethemwithadultAPC.UsingourpreviouslydescribedgatingstrategyforadulttissueAPC7,8(ExtendedDataFi...
