Interleukin-21 as a new therapeutic target for immune-mediated diseases

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tips.2009.05.006 Byline: Giovanni Monteleone (1), Francesco Pallone (1), Thomas T. Macdonald (2) Abstract: Cytokines have a decisive role in initiating and shaping pathologic responses in patients with various immune-inflammatory diseases. Recent studies indicate that interleukin (IL)-21, a cytokine produced mostly by activated CD4+ T cells, participates in the tissue damage in various tissues, owing to its ability to regulate the function of immune and non-immune cells. For instance, IL-21 controls the differentiation and functional activity of T cells, B cells and NK cells, limits the differentiation of inducible regulatory T cells (Tregs), and makes T cells resistant to the Treg-mediated immunesuppression. It also stimulates epithelial cells and fibroblasts to produce inflammatory mediators. Here, we focus on data supporting the pathogenic role of IL-21 in human inflammatory diseases and discuss pre-clinical studies that suggest that neutralization of IL-21 in vivo could be a new biological therapy to combat immune-mediated pathologies, such as inflammatory bowel diseases, diabetes, rheumatoid arthritis and systemic lupus erythematosus. Author Affiliation: (1) Department of Internal Medicine, University of Rome 'Tor Vergata', Rome 00133, Italy (2) Institute of Cell and Molecular Science, Bart's and the London School of Medicine and Dentistry, London, E1 2AT, UK