Primary B-Cell Deficiencies Reveal a Link between Human IL-17-Producing CD4 T-Cell Homeostasis and B-Cell Differentiation 英文参考文献.docVIP

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Primary B-Cell Deficiencies Reveal a Link between Human IL-17-Producing CD4 T-Cell Homeostasis and B-Cell Differentiation 英文参考文献.doc

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Primary B-Cell Deficiencies Reveal a Link between Human IL-17-Producing CD4 T-Cell Homeostasis and B-Cell Differentiation 英文参考文献

PrimaryB-CellDeficienciesRevealaLinkbetween HumanIL-17-ProducingCD4T-CellHomeostasisand B-CellDifferentiation RitaR.Barbosa1,SaraP.Silva1,2,SusanaL.Silva1,2,AlcindaCamposMelo1,ElisaPedro2,ManuelP. Barbosa2,M.Conceic?a?oPereira-Santos1,RuiM.M.Victorino1,2,AnaE.Sousa1* 1InstitutodeMedicinaMolecular,FaculdadedeMedicina,UniversidadedeLisboa,Lisboa,Portugal,2HospitaldeSantaMaria,CentroHospitalarLisboaNorte,Lisboa, Portugal Abstract IL-17isapro-inflammatorycytokineimplicatedinautoimmuneandinflammatoryconditions.Thedevelopment/survivalof IL-17-producingCD4Tcells(Th17)sharecriticalcueswithB-celldifferentiationandthecirculatingfollicularThelpersubset wasrecentlyshowntobeenrichedinTh17cellsabletohelpB-celldifferentiation.Weinvestigatedaputativelinkbetween Th17-cellhomeostasisandBcellsbystudyingtheTh17-cellcompartmentinprimaryB-cellimmunodeficiencies.Common VariableImmunodeficiencyDisorders(CVID),definedbydefectsinB-celldifferentiationintoplasmaandmemoryBcells,are frequentlyassociatedwithautoimmuneandinflammatorymanifestationsbutwefoundnorelationshipbetweentheseand Th17-cell frequency. In fact, CVID patients showed a decrease in Th17-cell frequency in parallel with the expansion of activatednon-differentiatedBcells(CD21lowCD38low).Moreover,CongenitalAgammaglobulinemiapatients,lackingBcells due to impaired early B-cell development, had a severe reduction of circulating Th17 cells. Finally, we found a direct correlation in healthy individuals between circulating Th17-cell frequency and both switched-memory B cells and serum BAFFlevels,acrucialcytokineforB-cellsurvival.Overall,ourdatasupportarelationshipbetweenTh17-cellhomeostasisand B-cellmaturation,withimplicationsfortheunderstandingofthepathogenesisofinflammatory/autoimmunediseasesand thephysiologyofB-celldepletingtherapies. Citation: Barbosa RR,Silva SP,Silva SL, Melo AC,PedroE,et al. (2011) Primary B-Cell Deficiencies Reveal aLink betweenHuman IL-17-ProducingCD4 T-Cell HomeostasisandB-CellDifferentiation.PLoSONE6(8):e22848