Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
The increased expression of IL‐23 in inflammatory bowel disease promotes intraepithelial and lamina propria lymphocyte inflammatory responses and cytotoxicity | |
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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