Rat bone marrow‐derived dendritic cells generated with GM‐CSF/IL‐4 or FLT3L exhibit distinct phenotypical and functional characteristics

[摘要] DendriticcellsareprofessionalAPCsthatplayacentralroleintheinitiationofimmuneresponses.Thelimitedexvivoavailabilityofdendriticcellsinspiresthewidespreaduseofbonemarrow‐deriveddendriticcellsasanalternativeinresearch.However,thefunctionalcharacteristicsofbonemarrow‐deriveddendriticcellsareincompletelyunderstood.Therefore,wecomparedfunctionalandphenotypiccharacteristicsofratbonemarrow‐deriveddendriticcellsgeneratedwithGM‐CSF/IL‐4orFLT3ligandbonemarrow‐deriveddendriticcells.AcomparisonofsurfacemarkersrevealedthatFLT3ligand‐bonemarrow‐deriveddendriticcellsexpressedsignalregulatoryproteinα,CD103,andCD4andbaselinelevelsofMHCclassII,CD40,andCD86,whichwerehighlyup‐regulateduponstimulation.Conversely,GM‐CSF/IL‐4‐bonemarrow‐deriveddendriticcellsconstitutivelyexpressedsignalregulatoryproteinα,CD11c,andCD11bbutonlymildlyup‐regulatedMHCclassII,CD40,orCD86followingstimulation.Expressionofdendriticcell‐associatedcoretranscriptswasrestrictedtoFLT3ligand‐bonemarrow‐deriveddendriticcells.GM‐CSF/IL‐4‐bonemarrow‐deriveddendriticcellsweresuperioratphagocytosisbutwereoutperformedbyFLT3ligand‐bonemarrow‐deriveddendriticcellsatantigenpresentationandTcellstimulationinvitro.StimulatedGM‐CSF/IL‐4‐bonemarrow‐deriveddendriticcellssecretedmoreTNF,CCL5,CCL20,andNO,whereasFLT3ligand‐bonemarrow‐deriveddendriticcellssecretedmoreIL‐6andIL‐12.Finally,whereasGM‐CSF/IL‐4‐bonemarrow‐deriveddendriticcellculturesupernatantsaddedtorestingTcellculturespromotedforkheadboxp3+regulatoryTcellpopulations,FLT3ligand‐bonemarrow‐deriveddendriticcellculturesupernatantsdroveTh17differentiation.WeconcludethatratGM‐CSF/IL‐4‐bonemarrow‐deriveddendriticcellsandFLT3ligand‐bonemarrow‐deriveddendriticcellsarefunctionallydistinct.OurdatasupportthecurrentrationalethatFLT3ligand‐bonemarrow‐deriveddendriticcellsmostlyresembleclassicdendriticcellsbutcompriseadditionalminorsubpopulations,whereasGM‐CSF/IL‐4‐bonemarrow‐deriveddendriticcellsresemblemonocyte‐derivedinflammatorydendriticcells(iNOS‐positivemonocyte‐derivedcells)...

[学科分类] 生理学

[关键词] antigen presentation;cytokines;phagocytosis;T cell stimulation;Th cell subsets