Il-21 enhances NK cell activation and cytolytic activity and induces Th17 cell differentiation in inflammatory bowel disease

✍ Scribed by Zhanju Liu; Li Yang; Yi Cui; Xingpeng Wang; Chuanyong Guo; Zhigang Huang; Quancheng Kan; Zhangsuo Liu; Yulan Liu

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 750 KB
• Volume: 15
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.20923

✦ Synopsis

Background: Interleukin-21 (IL-21) is involved in T and NK cell activation and effector response and promotes Th17 cell differentiation. Here we investigated IL-21 receptor (IL-21R) expression in 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-21R 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 realtime 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 ϩ , CD8 ϩ T, B, and NK cells. PB-NK cells from IBD patients produced higher levels of interferon gamma (IFN-␥) 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-␥) than controls when stimulated with IL-21 and anti-CD3. Importantly, IL-21 facilitated IBD CD4 ϩ T cell to differentiate into Th17 cells, characterized by increased expression of IL-17A and ROR␥t.

Conclusions: IL-21 enhances IBD NK cell cytotoxic response, triggers T cells to produce proinflammatory cytokines, and induces IBD CD4 ϩ 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.