Th22cellaccumulationisassociatedwithcolorectalcancerdevelopment

摘要： AIM:ToinvestigatetheexpressionofTh22cellsandrelatedcytokinesincolorectalcancer(CRC)tissues,andtheprobablymechanism.METHODS:CRCtumorandparatumortissueswerecollectedtodetecttheexpressionlevelsofTh22cellsandofrelatedcytokinesbyimmunohistochemistry,flowcytometryandreal-timequantitativepolymerasechainreaction(RT-qPCR).Interleukin(IL)-22aloneorwithaSTAT3inhibitorwasco-culturedwithRKOcellsinvitrotostudytheeffectsofIL-22oncoloncancercells.IL-22aloneorwithaSTAT3inhibitorwasinjectedintoaBALB/cnudemousemodelwithsubcutaneouslytransplantedRKOcellstostudytheeffectsofIL-22oncoloncancergrowth.RESULTS:ThepercentageofTh22cellsintheCD4+Tsubsetwassignificantlyhigherintumortissuescomparedwiththatinparatumortissues(1.47%±0.083%vs1.23%±0.077%,P<0.05)asdeterminedbyflowcytometry.RT-qPCRanalysisrevealedthatthemRNAexpressionlevelsofIL-22,arylhydrocarbonreceptor,CCL20andCCL22weresignificantlyhigherintumortissuescomparedwiththoseinparatumortissues.CCL27mRNAalsodisplayedahigherexpressionlevelintumortissuescomparedwiththatinparatumortissues;however,theselevelswerenotsignificantlydifferent(2.58±0.93vs2.30±0.78,P>0.05).IL-22enhancedcoloncancercellproliferationinvitroanddisplayedanti-apoptoticeffects;theseeffectswereblockedbyaddingaSTAT3inhibitor.IL-22promotedtumorgrowthinBALB/cnudemice;however,thiseffectwasreversedbyaddingaSTAT3inhibitor.CONCLUSION:Th22cellsthataccumulateinCRCmaybeassociatedwiththechemotacticeffectofthetumormicroenvironment.IL-22isassociatedwithCRCdevelopment,mostlikelyviaSTAT3activation. （共9頁(yè)）