The glucocorticoid dexamethasone programs human dendritic cells for enhanced phagocytosis of apoptotic neutrophils and inflammatory response

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

关键词: apoptophagocytic genes;    inflammation;    TNF‐;    α;    T cell activation;   

DOI  :  10.1189/jlb.0511243

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

GCsarepowerfulanti‐inflammatorycompoundsinhibitinginflammatorycellrecruitmentandproductionofproinflammatorycytokines.WehaverecentlyfoundthatDCs,thekeyplayersofTcellprimingandpolarization,respondtoallogeneicapoptoticneutrophilswithproinflammatorycytokinereleaseandTh1cellactivation.Here,weshowthatmonocyte‐derivedhumanDCsdeveloptheircapacitytoengulfapoptoticcellsbyup‐regulatingasetofapoptophagocyticgenes.ThisgeneexpressionpatternwasreprogrammedwhendifferentiationtookplaceinthepresenceofthesyntheticGCDex,whichincreasedtheexpressionofphagocytosisreceptorsMERTKandCD14,thebridgingmoleculeC1QA,DNASE2,andADORA3.TheincreasedphagocytosiswasattenuatedbytheadditionofADORA3antagonistandcouldnotbeobservedwhenbonemarrow‐derivedDCsofADORA3KOmiceweretreatedwithDex.TheGC‐treatedhumanDCsloadedwithallogeneicapoptoticneutrophilssecreted,inresponsetoLPSandIFN‐γ,theinflammatorycytokineTNF‐α.Furthermore,theDex‐treatedDCscouldactivateautologousTlymphocytestowardTh1effectorcells,andthiswasenhancedbytheirexposuretoallogeneicapoptoticneutrophils...

【 授权许可】

CC BY