The TWEAK/Fn14 pathway as an aggravating and perpetuating factor in inflammatory diseases; focus on inflammatory bowel diseases

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

关键词: Crohnˈ;    s disease;    ulcerative colitis;    TNF superfamily;    epithelial death;    inflammation;    tissue remodeling;   

DOI  :  10.1189/jlb.0112042

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TheTWEAK/Fn14pathwayisaligand/receptorpairoftheTNFSFthathasemergedasaprominentplayerinnormalandpathologicaltissueremodeling.TWEAK/Fn14pathwayactivationdrivesmanyprocessesrelevanttoautoimmuneandinflammatorydiseases.IBDs,includingCDandUC,arechronic,relapsinginflammatorydiseasesoftheGItract.Thesediseasesdifferintheirclinical,macroscopic,andhistopathologicalpresentation;however,pathologicalprocessesthatprominentlycontribute,moreorlessineachcase,includebreakdownofthemucosalepithelialbarrier,chronicinflammation,andtissueremodelingwithfibrosis.TWEAKmaypromotethepathogenesisofIBDbysignalingthroughFn14,whichcanbeup‐regulatedonIECs,therebycontributingtobreakdownofthemucosalbarrier;theinductionofIEC‐derivedmediatorsthatpromotechronicinflammationandshapegutimmunityagainstcommensalflora;anddelayedhealingandfibrosis.TWEAKmayalsoexertitsactiononendothelialandstromalcelltypes,includingsmoothmusclecellsandfibroblasts,topromotechronicinflammation,dysregulatedtissuerepair,andfibrosis.Here,wereviewthedatasupportinganemergingroleoftheTWEAK/Fn14pathwayinautoimmuneandinflammatorydiseases,withaparticularfocusonIBD,anddiscusshowitinterplayswithotherprominentpathways,includingIL‐13,TNF‐α,andTGF‐β,toaggravateandperpetuatethepathologicalprocessesunderlyingIBD...

【 授权许可】

CC BY