PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction 英文参考文献.docVIP

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PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction 英文参考文献.doc

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PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction 英文参考文献

Zhangetal.CriticalCare2010,14:R220 /content/14/6/R220 RESEARCH OpenAccess PD-L1blockadeimprovessurvivalinexperimental sepsisbyinhibitinglymphocyteapoptosisand reversingmonocytedysfunction YanZhang1?,YingZhou2?,JingshengLou3?,JinbaoLi3,LulongBo3,KemingZhu3,XiaojianWan3, XiaomingDeng3*,ZailongCai1* Abstract Introduction:Lymphocyteapoptosisandmonocytedysfunctionplayapivotalroleinsepsis-induced immunosuppression.Programmeddeath-1(PD1)anditsligandprogrammeddeathligand-1(PD-L1)exert inhibitoryfunctionbyregulatingthebalanceamongTcellactivation,tolerance,andimmunopathology.PD-1 deficiencyorblockadehasbeenshowntoimprovesurvivalinmurinesepsis.However,PD-L1andPD-1differin theirexpressionpatternsandtheroleofPD-L1insepsis-inducedimmunosuppressionisstillunknown. Methods:SepsiswasinducedinadultC57BL/6malemiceviacecalligationandpuncture(CLP).Theexpressionof PD-1andPD-L1expressiononperipheralTcells,Bcellsandmonocytesweremeasured24hoursafterCLPor shamsurgery.Additionally,theeffectsofanti-PD-L1antibodyonlymphocytenumber,apoptosisofspleenand thymus,activitiesofcaspase-8andcaspase-9,cytokineproduction,bacterialclearance,andsurvivalwere determined. Results:ExpressionofPD-1onTcells,BcellsandmonocytesandPD-L1onBcellsandmonocyteswereup- regulatedinsepticanimalscomparedtosham-operatedcontrols.PD-L1blockadesignificantlyimprovedsurvivalof CLPmice.Anti-PD-L1antibodyadministrationpreventedsepsis-induceddepletionoflymphocytes,increasedtumor necrosisfactor(TNF)-aandinterleukin(IL)-6production,decreasedIL-10production,andenhancedbacterial clearance. Conclusions:PD-L1blockadeexertsaprotectiveeffectonsepsisatleastpartlybyinhibitinglymphocyteapoptosis andreversingmonocytedysfunction.Anti-PD-L1antibodyadministrationmaybeapromisingtherapeuticstrategy forsepsis-inducedimmunosuppression. Introduction Sepsis, a systemic inflammatory response to infection, resultsinthedeathofmorethan210,000peopleinthe sepsis is important in identifying new therapeutic strategies. Protracted immunosuppression caused by im