Phagocytosis of apoptotic or necrotic cells differentially regulates the transcriptional expression of IL‐12 family members in dendritic cells

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

关键词: dendritic cells;    cytokines;    tolerance;   

DOI  :  10.1189/jlb.3A1013-538RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

UptakeofapoptoticcellsbyDCsisconsideredtocontributetoinductionandmaintenanceofimmunologicaltolerance.TolDCsaresoughtafterascellulartherapyintransplantationandautoimmunityandcanbegeneratedinvitrousingGCs.Inthisstudy,weinvestigatedhowuptakeofdeadcellsaffectstheproductionandexpressionofdifferentmembersoftheIL‐12familybyimmatureDCsorTolDCs.WeshowthatcomparedtoregularimmatureDCs,TolDCsdisplayelevatedlevelsofPS‐recognizingbridgemoleculereceptorsαvβ5andCD36,andhaveenhancedphagocyticabilitieswithaccelerateduptakeofapoptoticcells.WeconfirmthatapoptoticcelluptakeresultsindiminishedproductionofIL‐12p40andIL‐12p70byDCs.WenowshowthatthisalsoresultsinincreasedexpressionofIL‐12p35andEbi3.TolDCscompletelylackexpressionofIL‐12p40yethaveenhancedlevelsofEbi3andIL‐12p35.UptakebyTolDCsofapoptoticornecroticcellsdoesnotaffecttheexpressionofEbi3/IL‐12p35andalsodoesnotincreaseIL‐12p40.ThisisdistinctfromthecultureofimmatureDCswithnecroticcells,whichissufficienttoinduceIL‐12p40secretion.Conversely,ingestionofapoptoticcellsbyDCsleadstoincreasedexpressionofIL‐12p35andEbi3withoutaffectingIL‐12p40.Inconclusion,wehaveshownthatuptakeofapoptoticversusnecroticcellsbyDCsdifferentiallyregulatesmembersoftheIL‐12family.ApoptoticcellsfavorexpressionofEbi3andIL‐12p35,andweproposethatdifferentialregulationoftheIL‐12familyisanadditionalmechanismindeterminingtheimmuneresponsetodyingcells...

【 授权许可】

CC BY