Monocytes differentiated with GM‐CSF and IL‐15 initiate Th17 and Th1 responses that are contact‐dependent and mediated by IL‐15

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

关键词: human immunology;    TLRs;    IL‐;    1β;    IL‐;    23;    inflammation;   

DOI  :  10.1189/jlb.0311132

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

DistincttypesofDCsaregeneratedfrommonocytesusingGM‐CSFwithIL‐4(IL4‐DC)orIL‐15(IL15‐DC).IL15‐DCsarepotentinducersofantigen‐specificCD8+Tcells,displayaphenotypesimilartoCD14+cellscommonlydescribedinchronicallyinflamedtissues,andproducehighlevelsofIL‐1βandIL‐15inresponsetoTLR4stimulation.AsthesecytokinespromoteTh17responses,whicharealsoassociatedwithinflammatorydiseases,IhypothesizedthatTLR‐primedIL15‐DCsfavorTh17activationoverIL4‐DCs.ComparedwithIL4‐DCs,IL15‐DCsstimulatedwithTLRagonistssecretedsignificantlyhigherconcentrationsoftheTh17‐promotingfactors,IL‐1β,IL‐6,IL‐23,andCCL20,andlowerlevelsoftheTh1cytokine,IL‐12.Inaddition,IL15‐DCsandnotIL4‐DCsup‐regulatedIL‐15onthecellsurfaceinresponsetoTLRagonists.IL15‐DCsprimedwithTLR3orTLR4agoniststriggeredTh17(IL‐17,IL‐22,and/orIFN‐γ)andTh1(IFN‐γ)responses,whereasIL4‐DCsprimedwiththesameTLRagonistsactivatedTh1(IFN‐γ)responses.SecretionofIL‐17andIFN‐γrequiredcontactwithTLR‐primedIL15‐DC,andIFN‐γproductionwasmediatedbymembrane‐boundIL‐15.Thesefindingsidentifykeydifferencesinmonocyte‐derivedDCs,whichimpactadaptiveimmunity,andprovideprimaryevidencethatIL‐15promotesTh17andTh1responsesbyskewingmonocytesintoIL15‐DC...

【 授权许可】

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