A requirement of dendritic cell‐derived interleukin‐27 for the tumor infiltration of regulatory T cells

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

关键词: cytokine;    lymphocytes;    chemotaxis;    immunology;   

DOI  :  10.1189/jlb.0713371

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Tregs(Foxp3+CD4+)areenrichedintumorstofosteratolerantmicroenvironmentthatinhibitsantitumorimmuneresponse.IL‐27isreportedtoregulatethedevelopmentandfunctionofTregsinvitroandinvivo;however,theeffectsofendogenousIL‐27onTregsinthetumormicroenvironmentremainelusive.WedemonstratedthatintheabsenceofDC‐derivedIL‐27,TregsweredecreasedsignificantlyintransplantedB16melanoma,transplantedEL‐4lymphoma,andMCA‐inducedfibrosarcomabyusingIL‐27p28conditionalKOmice.FurtherstudiesrevealedthatIL‐27promotedtheexpressionofCCL22,whichisestablishedtomediatetherecruitmentofperipheralTregsintotumors.Tumor‐associatedDCswereidentifiedasthemajorsourceofCCL22intumorsites,andIL‐27couldinduceCCL22expressioninanIL‐27R‐dependentmanner.IntratumoralreconstitutionofrmCCL22orrmIL‐27,butnotrmIL‐27p28,significantlyrestoredthetumorinfiltrationofTregsinIL‐27p28KOmice.CorrelatedwithadecreasednumberofTregs,tumor‐infiltratingCD4TcellswerefoundtoproducemuchmoreIFN‐γinIL‐27p28KOmice,whichhighlightedthephysiologicalimportanceofTregsinsuppressinganantitumorimmuneresponse.Overall,ourresultsidentifiedanovelmechanismofactionofIL‐27onTregsinthecontextofcancers...

【 授权许可】

CC BY