Targeting interleukin-21 in immune-mediated pathologies.
Interleukin (IL)-21, a cytokine mostly produced by activated CD4+ T cells, has been reported to play an important role in the tissue-damaging immune response in various organs. This pathogenic effect is strictly linked to the ability of IL-21 to control the functional activities of multiple immune and non-immune cells. For instance, IL-21 regulates the differentiation and function of effector CD4+ T helper cells; controls activation, proliferation, and survival of B cells and enhances the cytotoxic activity of CD8+ T cells and NK cells. IL-21 also inhibits the differentiation of inducible regulatory T cells (Tregs) and makes effector CD4+ T cells resistant to the Tregs-mediated immunesuppression. Additionally, IL-21 stimulates epithelial cells and fibroblasts to make chemokines and extracellular matrix proteases, respectively. Consistently, studies from various laboratories have documented the beneficial effect of IL-21 neutralization on the progression of inflammatory diseases in mice. Here we review the present knowledge on the expression and role of IL-21 in immune-mediated pathologies.
Sarra
Massimiliano
M
Department of Internal Medicine, University of Rome "Tor Vergata", Rome, Italy.
Pallone
Francesco
F
Macdonald
Thomas T
TT
Monteleone
Giovanni
G
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015551:Autoimmunity / Q000235:genetics; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy* / Q000378:metabolism; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D053655:Receptors, Interleukin-21 / Q000235:genetics; D000098546:Interleukin-21
D000893:Anti-Inflammatory Agents; D007378:Interleukins; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21