title: Il-21 enhances NK cell activation and cytolytic activity and induces Th17 cell differentiation in inflammatory bowel disease.
abstract: 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 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.
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. zhanjuliu@yahoo.com
authors.forename: Zhanju
authors.initials: Z
authors.lastname: Liu
authors.forename: Li
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authors.lastname: Yang
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authors.lastname: Liu