MGL signaling augments TLR2‐mediated responses for enhanced IL‐10 and TNF‐α secretion

[摘要] DCsorchestrateimmuneresponsestoinfectiouspathogensanddisturbancesintissueintegrity.EquippedwithC‐typelectins,DCscanrespondtoenvironmentalchangesinglycosylation.ManyC‐typelectinsarecapableofmodulatingTLRactivation,therebyfacilitatingtailor‐madeimmunereactions.Here,weinvestigatedthesignalingpropertiesoftheC‐typelectinMGLandshowthatMGLengagementbyagonisticantibodiesorcarbohydrateligandscouplestoTLRsignaltransductionforincreasedIL‐10andTNF‐αsecretionbyhumanmonocyte‐derivedDCs.MGLtriggeringespeciallysynergizedwithTLR2‐inducedpathways,leadingtoelevatedIL‐10mRNAlevelsandenhancedTNF‐αmRNAstability.Inaddition,MGLsignalingpromotedphosphorylationoftheMAPKERKandthetranscriptionfactorCREB.Whereasspecificinhibitorsofp90RSKblockedtheMGL‐inducedcytokinesecretion,AP‐1wasnotinvolved.Strikingly,NF‐κBwasonlycrucialfortheIL‐10responseanddispensableforTNF‐αproduction.Together,ourresultsdemonstratethatMGLactivationoftheERK‐p90RSK‐CREBaxisconvergeswithTLR2‐inducedpathways,therebyfine‐tuningtheDCmaturationphenotype...

[学科分类] 生理学

[关键词] dendritic cells;C‐type lectin;macrophage galactose‐type lectin;Tn antigen