Perturbed MafB/GATA1 axis after burn trauma bares the potential mechanism for immune suppression and anemia of critical illness

[摘要] Patientswhosurviveinitialburninjuryaresusceptibletonosocomialinfections.Anemiaofcriticalillnessisacompoundingfactorinburnpatientsthatnecessitatesrepeatedtransfusions,whichfurtherincreasetheirsusceptibilitytoinfectionsandsepsis.Robusthostresponseisdependentonanadequatenumberandfunctionofmonocytes/macrophagesanddendriticcells.InadditiontoimpairedRBCproduction,burnpatientsarepronetodepletionofdendriticcellsandanincreaseindeactivatedmonocytes.Insteady‐statehematopoiesis,RBCs,macrophages,anddendriticcellsareallgeneratedfromacommonmyeloidprogenitorwithinthebonemarrow.Wehypothesizedinamousemodelofburninjurythatanincreaseinmyeloid‐specifictranscriptionfactorV‐mafmusculoaponeuroticfibrosarcomaoncogenehomologBatthecommonmyeloidprogenitorstagesteerstheirlineagepotentialawayfromthemegakaryocyteerythrocyteprogenitorproductionanddrivestheterminalfateofcommonmyeloidprogenitorstoformmacrophagesvs.dendriticcells,withtheconsequencesbeinganemia,monocytosis,anddendriticcelldeficits.Resultsindicatethat,eventhoughburninjurystimulatedbonemarrowhematopoiesisbyincreasingmultipotentialstemcellproduction(LinnegSca1poscKitpos),thebonemarrowcommitmentisshiftedawayfromthemegakaryocyteerythrocyteprogenitorandtowardgranulocytemonocyteprogenitorswithcorrespondingalterationsinperipheralbloodcomponents,suchashemoglobin,hematocrit,RBCs,monocytes,andgranulocytes.Furthermore,burn‐inducedV‐mafmusculoaponeuroticfibrosarcomaoncogenehomologBincommonmyeloidprogenitorsactsasatranscriptionalactivatorofM‐CSFRandarepressoroftransferrinreceptors,promotingmacrophagesandinhibitingerythroiddifferentiationswhiledictatingaplasmacytoiddendriticcellphenotype.ResultsfromsmallinterferingRNAandgain‐of‐function(gfp‐globintranscriptionfactor1retrovirus)studiesindicatethattargetedinterventionstorestoreV‐mafmusculoaponeuroticfibrosarcomaoncogenehomologB/globintranscriptionfactor1balancecanmitigatebothimmuneimbalanceandanemiaofcriticalillness...

[学科分类] 生理学

[关键词] hematopoiesis;CMP;MEP;dendritic cell;macrophages