Severe Thymic Atrophy in a Mouse Model of Skin Inflammation Accounts for Impaired TNFR1 Signaling 英文参考文献.docVIP

Severe Thymic Atrophy in a Mouse Model of Skin Inflammation Accounts for Impaired TNFR1 Signaling 英文参考文献.doc

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Severe Thymic Atrophy in a Mouse Model of Skin Inflammation Accounts for Impaired TNFR1 Signaling 英文参考文献

SevereThymicAtrophyinaMouseModelofSkin InflammationAccountsforImpairedTNFR1Signaling NathalieBelhace′ne1,4,5,ParvatiGamas1,4,5,DiogoGonc?alve`s1,4,5,MarieJacquin2,4,MarieBeneteau2,4 , ArnaudJacquel1,4,5,PascalColosetti1,4,5,Jean-EhrlandRicci2,4,AbdellilahWakkach3,4 , PatrickAuberger1,4,5.,SandrineMarchetti 1,4,5 . * 1Inserm, UMR 1065, Centre Me′diterrane′en de Me′decine Mole′culaire, Team ?Cell death, differentiation, inflammation and cancer?, Nice, France, 2Inserm, UMR 1065, CentreMe′diterrane′endeMe′decineMole′culaire,Team?Metaboliccontrolofcelldeaths?,Nice,France,3CNRS,FRE3472,LP2M,Nice,France,4Universite′ deNiceSophia Antipolis,Faculte′ deMe′decine,Nice,France,5Equipelabellise′eparlaLigueNationaleContreleCancer2011–2013,Paris,France Abstract Transgenicmiceexpressingthecaspase-cleavedformofthetyrosinekinaseLyn(LynDN)developaTNFa-dependentskin disease that accurately recapitulates human psoriasis. Participation of lymphocytes in this disease was confirmed by backcrossingLynDNmiceonaRag-1deficientbackground.Thepresentstudywasthereforeconductedtoanalyzewhether modificationoflymphocytehomeostasisdoesoccurandparticipateinthephenotypeofLynDNmice.Weshowherethat LynDNmiceconsistentlyexhibitthymicatrophythatcorrelateswithbothanetdecreaseintheCD4+/CD8+DoublePositive (DP)andanincreaseinSinglePositive(SP)thymocytesub-populations,butalsodisplayanincreaseofsplenicmatureBcell. Interestingly,anormalimmunephenotypewasrescuedinaTNFR1deficientbackground.Finally,noneoftheseimmune alterations was detected in newborn mice before the onset of inflammation. Therefore, we conclude that chronic inflammationcaninducethymicatrophyandperturbspleenhomeostasisinLynDNmicethroughtheincreasedproduction ofTNFa,LT?andTNFR1signaling. Citation:Belhace′neN,GamasP,Gonc?alve`s D,JacquinM,BeneteauM,etal.(2012)SevereThymicAtrophyinaMouseModelofSkinInflammationAccountsfor ImpairedTNFR1Signaling.PLoSONE7(10):e47321.doi:10.1371/journal.pone.0047321 Editor:SebastienFuchs,Cedars-SinaiMedicalCente

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