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学科主题: 临床医学
题名:
IL-21 Enhances NK Cell Activation and Cytolytic Activity and Induces Th17 Cell Differentiation in Inflammatory Bowel Disease
作者: Liu, Zhanju1; Yang, Li1; Cui, Yi1; Wang, Xingpeng1; Guo, Chuanyong1; Huang, Zhigang1; Kan, Quancheng2; Liu, Zhangsuo2; Liu, Yulan3
关键词: IL-21 ; Crohn&prime ; s disease ; ulcerative colitis ; inflammatory bowel disease ; NK cell ; Th17
刊名: INFLAMMATORY BOWEL DISEASES
发表日期: 2009-08-01
DOI: 10.1002/ibd.20923
卷: 15, 期:8, 页:1133-1144
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology
研究领域[WOS]: Gastroenterology & Hepatology
关键词[WOS]: RHEUMATOID-ARTHRITIS ; INTERLEUKIN-21 RECEPTOR ; CYTOKINE PRODUCTION ; CROHNS-DISEASE ; ANIMAL-MODELS ; T(H)17 CELLS ; T-CELLS ; EXPRESSION ; AUTOIMMUNITY ; EXPANSION
英文摘要:

Background: Interleukin-21 (IL-21) is involved ill T and NK cell activation and effector response and promotes Th17 cell differentiation. Here we investigated IL-21 receptor (IL-21R) expression ill inflamed mucosa of inflammatory bowel disease (IBD) and evaluated its role in the induction of NK cell cytotoxicity and activation as well as Th17 differentiation.

Methods: Expression of IL-21 R was performed by immunohistochemistry and flow cytometry. NK cell cytotoxicity was detected by a standard (51)Cr-release assay. Cytokine levels were analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (PCR).

Results: IL-21R-positive cells were significantly increased in inflamed mucosa of IBD compared with controls, and mainly expressed in freshly isolated peripheral blood (PB)- and lamina propria (LP)-CD4(+), CD8(+) T, B, and NK cells. PB-NK cells from IBD patients produced higher levels of interferon gamma (IFN-gamma) and tumor necrosis factor (TNF) than controls when stimulated with immobilized human IgG and IL-21. IL-21-primed IBD NK cells showed a more potent antitumor cytotoxicity to NK-sensitive K562 cells than controls. Moreover, PB-T and LP-T cells from IBD patients produced large amounts of proinflammatory cytokines (e.g., TNF, IFN-gamma) than controls when stimulated with IL-21 and anti-CD3. Importantly, IL-21 facilitated IBD CD4(+) T cell to differentiate into Th17 cells, characterized by increased expression of IL-17A and ROR gamma t.

Conclusions: IL-21 enhances IBD NK cell cytotoxic response. triggers T cells to produce proinflammatory cytokines, and induces IBD CD4(+) T cells to differentiate into Th17 cells, suggesting that IL-21 is involved in the pathogenesis of IBD and that blocking IL-21R signaling may have a therapeutic potential in IBD.

语种: 英语
所属项目编号: 30571751 ; 30770988 ; NECT-05-0609
项目资助者: National Natural Science Foundation of China ; Program for New Century Excellent Talents in University China
WOS记录号: WOS:000268869000007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63092
Appears in Collections:北京大学第二临床医学院_消化内科_期刊论文

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作者单位: 1.Tongji Univ, Shanghai Peoples Hosp 10, Dept Gastroenterol, Sch Med, Shanghai 200072, Peoples R China
2.Zhengzhou Univ, Affiliated Hosp 1, Lab Clin Res, Zhengzhou, Peoples R China
3.Beijing Univ, Peoples Hosp, Dept Gastroenterol, Beijing 100871, Peoples R China

Recommended Citation:
Liu, Zhanju,Yang, Li,Cui, Yi,et al. IL-21 Enhances NK Cell Activation and Cytolytic Activity and Induces Th17 Cell Differentiation in Inflammatory Bowel Disease[J]. INFLAMMATORY BOWEL DISEASES,2009,15(8):1133-1144.
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