IL-21 was first described as a critical regulator of T- and B-cell functions. More recently, it has become apparent that IL-21 controls the activity of both immune and nonimmune cells and, depending on the timing and context analyzed, it can promote either inflammatory or counter-regulatory effects. IL-21 participates in the immune responses against tumor cells and chronic viral infections, but excessive production of IL-21 has been associated with the development of immune-inflammatory diseases in various organs. In this article, we focus on data supporting the pathogenic role of IL-21 in human inflammatory bowel diseases and discuss preclinical studies that suggest that neutralization of IL-21 in vivo could be a new strategy to counteract the inflammatory bowel disease-related, tissue damaging immune response.
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