Replenishment of the B cell compartment after doxorubicin‐induced hematopoietic toxicity is facilitated by STAT1

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

关键词: lymphocyte development;    pro‐;    B cells;    Sca‐;    1;    IFN‐;    γ;    IL‐;    7;   

DOI  :  10.1189/jlb.0113053

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

STAT1servesasanimportantregulatorintheresponsetopathogens,oncogenictransformation,andgenotoxicinsults.Itexertstheseeffectsbyshapingtheinnateandadaptiveimmuneresponseandbyparticipatingingenotoxicstresspathways,leadingtoapoptosisandinhibitionofcellproliferation.WehaveinvestigatedtheroleofSTAT1inhematopoietictoxicityinducedbydoxorubicininSTAT1‐proficientand‐deficientmice.WhereastheearlygenotoxiceffectofdoxorubicindidnotdependonSTAT1,expressionofSTAT1wasrequiredforefficientBlymphocyterepopulationintherecoveryphase.WefoundalowerabundanceoflymphocyteprecursorsintheBMofSTAT1‐deficientanimals,whichwasparticularlyevidentafterdoxorubicin‐inducedhematopoietictoxicity.Inaccordance,colony‐formingassayswithSTAT1‐deficientBMcellsrevealedadecreasednumberofpre‐Bcolonies.Differentiationfromthepro‐Btothepre‐Bstagewasnotaffected,asdemonstratedbyunaltereddifferentiationofpurifiedBcellprecursorsfromBMinthepresenceofIL‐7.WiththeexceptionofSca‐1,expressionofgenesimplicatedinearlylymphocytedevelopmentinpro‐BcellsdidnotdependonSTAT1.OurfindingsindicateaspecificrequirementforSTAT1inlymphoiddevelopmentbeforedifferentiationtopre‐Bcells,whichbecomesparticularlyapparentintherecoveryphasefromdoxorubicin‐inducedhematopoietictoxicity...

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