Human blood CD1c dendritic cells stimulate IL‐12‐independent IFN‐γ responses and have a strikingly low inflammatory profile

[摘要] AdaptiveimmuneresponsesareinitiatedbyresidentmyeloidtissueDC.AmajorfractionoftissueDCexpressCD1c+andisthoughttobederivedfrombloodCD1cDC,anideasupportedherebytheobservationthattheyexpresstissue‐homingmoleculesandrapidlydifferentiateintocellswithatissueDCphenotype.Responsesarethoughttobeaugmented/modulatedfurtherbyinflammatorymoDC.AlthoughmuchacceptedhumanmyeloidDCcellbiologyisbasedonmoDCstudies,wefindthese2DCpopulationstobefunctionallydistinct.StimulatedmoDCproducehighlevelsofIL‐10andtheTh1‐promotingcytokineIL‐12.Underidenticalconditions,CD1cDCsynthesizednoIL‐10andnoorlowlevelsofIL‐12.Despitethis,CD1cDCstimulatedastrongTh1response,demonstratedbyIL‐12neutralizationtobeIL‐12independent,whereastheresponseinducedbymoDCwasIL‐12dependent.ThisfindingwassupportedbystudiesonapatientwithahighlyreducedabilitytosynthesizeIL‐12,whoseCD1cDCinducedagoodTh1responsecontrastingwiththefailureofhismoDC,whichwereimpairedinIL‐12production,toinduceIFN‐γ‐secretingTcells.TheIL‐10andIL‐12datawereconfirmedbymicroarrayanalysis,whichalsoshowedthatstimulatedmoDCproducedinflammatory‐associatedchemokinesandcytokines,whereasstimulatedCD1cDCshowedminimalup‐regulationofthesegenes.Thus,moDC,widelyusedasahumanmyeloidDCmodel,donotfaithfullyreflectthepropertiesofCD1ctissueDC,makingtheinitialresponsetoapathogenorvaccine...

[学科分类] 生理学

[关键词] microarray;cytokines;monocyte;Th1