Prostaglandin E2 imprints a long‐lasting effect on dendritic cell progenitors in the bone marrow

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

关键词: Immunosuppression;    inflammation;    chimeric mice;    macrophages;    UV irradiation;    hemopoietic stem cells;   

DOI  :  10.1189/jlb.0513294

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Dendriticcells(DCs)thatdifferentiateinvitrofromthebonemarrow(BM)ofmicewithprostaglandinE2(PGE2)‐associatedinflammationoftheskin,airways,orperitonealcavitypoorlyinitiateimmuneresponses.ToremoveinvitrodifferentiationandallowBM‐derivedDCstoseedtheperipheryundersteady‐stateconditions,aswellasstudythemoleculeproposedresponsible,chimericmicewereengraftedfor>16wkwithBMcellsfrommiceexposedtoPGE2.SerialPGE2‐chimericmicewereestablishedwithBMcellsfromtheprimarychimericmice.ImmuneresponsesintheairwaysandskinofthePGE2‐chimericmiceandserialPGE2‐chimericmiceweresignificantlyattenuated.AfterinflammatorychallengesbyintranasalLPS,topicalfluoresceinisothiocyanate,andintraperitonealalum,DCs,macrophages,andneutrophilstraffickedpoorlyinPGE2‐chimericmiceandserialPGE2‐chimericmice.InjectionofBM‐differentiatedDCsfromnonchimericmicerestoredthereducedimmuneresponsesofPGE2‐chimericmice.DCsfromBMof16‐wk‐engraftedPGE2‐chimericandserialPGE2‐chimericmiceresembledcellsdifferentiatedfromBMexposedtoPGE2foronly3d,demonstratingthelong‐lastingeffectofPGE2onDCprogenitors.PGE2attenuatessystemicimmuneresponsesbymodulatingmyeloidcellprogenitorsintheBMsuchthatBM‐derived,terminallydifferentiatedmyeloidcellshavepoortraffickingabilitytositesofneed...

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