Overrepresentation of IL-17A and IL-22 Producing CD8 T Cells in Lesional Skin Suggests Their Involvement in the Pathogenesis of Psoriasis 英文参考文献.docVIP

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Overrepresentation of IL-17A and IL-22 Producing CD8 T Cells in Lesional Skin Suggests Their Involvement in the Pathogenesis of Psoriasis 英文参考文献.doc

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Overrepresentation of IL-17A and IL-22 Producing CD8 T Cells in Lesional Skin Suggests Their Involvement in the Pathogenesis of Psoriasis 英文参考文献

OverrepresentationofIL-17AandIL-22ProducingCD8T CellsinLesionalSkinSuggestsTheirInvolvementinthe PathogenesisofPsoriasis PieterC.M.Res1*,GamzePiskin1,OnnoJ.deBoer2,ChrisM.vanderLoos2,PeterTeeling2,JanD.Bos1, MarcelB.M.Teunissen1* 1DepartmentofDermatology,AcademicMedicalCenter,UniversityofAmsterdam,Amsterdam,TheNetherlands,2DepartmentofPathology,AcademicMedicalCenter, UniversityofAmsterdam,Amsterdam,TheNetherlands Abstract Background:AlthoughrecentstudiesindicateacrucialroleforIL-17AandIL-22producingTcellsinthepathogenesisof psoriasis,limitedinformationisavailableontheirfrequencyandheterogeneityandtheirdistributioninskininsitu. Methodology/PrincipalFindings:Byspectralimaginganalysisofdouble-stainedskinsectionswedemonstratedthatIL-17 wasmainlyexpressedbymastcellsandneutrophilsandIL-22bymacrophagesanddendriticcells.OnlyanoccasionalIL- 17pos,butnoIL-22posTcellcouldbedetectedinpsoriaticskin,whereasneitherofthesecytokineswasexpressedbyTcells innormalskin.However,examinationofinvitro-activatedTcellsbyflowcytometryrevealedthatsubstantialpercentagesof skin-derivedCD4andCD8TcellswereabletoproduceIL-17AaloneortogetherwithIL-22(i.e.Th17andTc17,respectively) ortoproduceIL-22inabsenceofIL-17AandIFN-c(i.e.Th22andTc22,respectively).Remarkably,asignificantproportional riseinTc17andTc22cells,butnotinTh17andTh22cells,wasfoundinTcellsisolatedfrompsoriaticversusnormalskin. Interestingly,wefoundIL-22single-producersinmanyskin-derivedIL-17AposCD4andCD8Tcellclones,suggestingthatin vivoIL-22single-producersmayarisefromIL-17Apos Tcellsaswell. Conclusions/Significance:TheincreasedpresenceofTc17andTc22cellsinlesionalpsoriaticskinsuggeststhatthesetypes ofCD8Tcellsplayasignificantroleinthepathogenesisofpsoriasis.Aspartoftheskin-derivedIL-17AposCD4andCD8T clonesdevelopedintoIL-22single-producers,thisdemonstratesplasticityintheircytokineproductionprofileandsuggests adevelopmentalrelationshipbetweenTh17andTh22cellsandbetweenTc17andTc22cells. Citation:ResPCM,PiskinG,deBoerOJ,vanderLoosCM,Teelin