title: The increased expression of IL-23 in inflammatory bowel disease promotes intraepithelial and lamina propria lymphocyte inflammatory responses and cytotoxicity.
abstract: This study analyzed IL-23p19 expression in inflamed mucosa of IBD and the role in the induction of IEL and NK cell activation as well as Th17 cell differentiation. Expression of IL-23p19 was performed by immunohistochemistry and quantitative real-time PCR. Expression of IL-23R was assessed by flow cytometry. Cytolytic activities of IEL and NK cells by IL-23 were determined by a standard (51)Cr-release assay. Cytokine levels were analyzed by ELISA and quantitative real-time PCR. Expression of IL-23p19 was increased significantly in inflamed mucosa of CD compared with that in UC and healthy controls. Double-staining confirmed that IL-23p19(+) cells were mainly CD68(+) macrophages/DCs. IL-23R(+) cells were increased significantly in PB- and LP-CD4(+) and -CD8(+) T and NK cells. IL-23 markedly promoted IBD IEL and NK cell activation and cytotoxicity and triggered IBD PB- and LP-T cells to secrete significantly higher levels of IFN-γ, TNF, IL-2, and IL-17A compared with controls. Importantly, IL-23 promoted IBD PB- or LP-CD4(+) T cells to differentiate into Th17 cells, characterized by increased expression of IL-17A and RORC. Anti-TNF treatment could markedly reduce IL-23 expression and Th17 cell infiltration in inflamed mucosa of CD patients. These data indicate that IL-23 is highly expressed in inflamed mucosa of IBD and plays an important role in the induction of IEL, NK, and T cell activation, proinflammatory cytokine secretion, and Th17 cell differentiation. Targeted therapy directed against IL-23p19 may have a therapeutic role in treatment of IBD.
authors.affiliation: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China. zhanjuliu@yahoo.com
authors.forename: Zhanju
authors.initials: Z
authors.lastname: Liu
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Yadav
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Xu
authors.forename: Jingling
authors.initials: J
authors.lastname: Su
authors.forename: Chi
authors.initials: C
authors.lastname: Chen
authors.forename: Maochun
authors.initials: M
authors.lastname: Tang
authors.forename: Hui
authors.initials: H
authors.lastname: Lin
authors.forename: Jifeng
authors.initials: J
authors.lastname: Yu
authors.forename: Jiaming
authors.initials: J
authors.lastname: Qian
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism*; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D020381:Interleukin-17 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058504:Th17 Cells
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D007376:Interleukin-2; D053760:Interleukin-23 Subunit p19; D012333:RNA, Messenger