The increased expression of IL‐23 in inflammatory bowel disease promotes intraepithelial and lamina propria lymphocyte inflammatory responses and cytotoxicity

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

关键词: Crohnˈ;    s disease;    mononuclear cell;    ulcerative colitis;   

DOI  :  10.1189/jlb.0810456

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThisstudyanalyzedIL‐23p19expressionininflamedmucosaofIBDandtheroleintheinductionofIELandNKcellactivationaswellasTh17celldifferentiation.ExpressionofIL‐23p19wasperformedbyimmunohistochemistryandquantitativereal‐timePCR.ExpressionofIL‐23Rwasassessedbyflowcytometry.CytolyticactivitiesofIELandNKcellsbyIL‐23weredeterminedbyastandard51Cr‐releaseassay.CytokinelevelswereanalyzedbyELISAandquantitativereal‐timePCR.ExpressionofIL‐23p19wasincreasedsignificantlyininflamedmucosaofCDcomparedwiththatinUCandhealthycontrols.Double‐stainingconfirmedthatIL‐23p19+cellsweremainlyCD68+macrophages/DCs.IL‐23R+cellswereincreasedsignificantlyinPB‐andLP‐CD4+and‐CD8+TandNKcells.IL‐23markedlypromotedIBDIELandNKcellactivationandcytotoxicityandtriggeredIBDPB‐andLP‐TcellstosecretesignificantlyhigherlevelsofIFN‐γ,TNF,IL‐2,andIL‐17Acomparedwithcontrols.Importantly,IL‐23promotedIBDPB‐orLP‐CD4+TcellstodifferentiateintoTh17cells,characterizedbyincreasedexpressionofIL‐17AandRORC.Anti‐TNFtreatmentcouldmarkedlyreduceIL‐23expressionandTh17cellinfiltrationininflamedmucosaofCDpatients.ThesedataindicatethatIL‐23ishighlyexpressedininflamedmucosaofIBDandplaysanimportantroleintheinductionofIEL,NK,andTcellactivation,proinflammatorycytokinesecretion,andTh17celldifferentiation.TargetedtherapydirectedagainstIL‐23p19mayhaveatherapeuticroleintreatmentofIBD...

【 授权许可】

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