High MafB expression following burn augments monocyte commitment and inhibits DC differentiation in hemopoietic progenitors

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

关键词: mDC;    GMP;    M‐;    CSF receptors;    LSK;    GATA‐;    1;    bone marrow;   

DOI  :  10.1189/jlb.0711338

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Wehavepreviouslyshownthatperturbedbonemarrowprogenitordevelopmentpromoteshyporesponsivemonocytesfollowingexperimentalburnsepsis.ClinicalandexperimentalsepsisisassociatedwithmonocytedeactivationanddepletionofmDCs.DecreaseincirculatingDCsisreportedinburnpatientswhodevelopsepsis.Inour15%TBSAscaldburnmodel,wedemonstrateasignificantreductioninthecirculatingMHC‐II+populationandmDCs(Gr1negCD11b+CD11c+)withacorrespondingdecreaseinbonemarrowMHC‐II+cellsandmDCsforupto14daysfollowingburn.Weexploredtheunderlyingmechanism(s)thatregulatebonemarrowdevelopmentofmonocytesandDCsfollowingburninjury.WefoundarobustbonemarrowresponsewithasignificantincreaseinmultipotentialHSCs(LSK)andbipotentialGMPsfollowingburninjury.GMPsfromburnmiceexhibitasignificantreductioninGATA‐1,whichisessentialforDCdevelopment,butexpresshighlevelsofMafBandM‐CSFRs,bothassociatedwithmonocyteproduction.GMPsobtainedfromburnmicedifferentiated1.7timesmoreintoMφand1.6‐foldlessintoDCscomparedwithsham.MonocytesandDCsexpressed50%lessMHC‐IIinburnversussham.IncreasedmonocytecommitmentinburnGMPswasaresultofhighMafBandM‐CSFRexpressions.TransientsilencingofMafB(siRNA)inGMP‐derivedmonocytesfromburnmicepartiallyrestoredDCdifferentiationdeficitsandincreasedGATA‐1expression.WeprovideevidencethathighMafBfollowingburnplaysaninhibitoryroleinmonocyte‐derivedDCdifferentiationbyregulatingM‐CSFRandGATA‐1expressions...

【 授权许可】

CC BY