title: IL-21 as a therapeutic target in inflammatory disorders.
abstract: BACKGROUND
  IL-21, a cytokine produced by activated CD4(+) cells, activated natural killer T cells and T helper cells in the germinal centers, is involved in the control of the function of both immune and parenchymal cells.
  
  
  METHODS
  IL-21 is overproduced in many chronic inflammatory disorders, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, type I diabetes and systemic lupus erythematosus, and studies in experimental models indicate that IL-21 plays an important role in sustaining tissue-damaging immune responses in such pathologies. However, genetic deficiency of IL-21 associates with inflammatory bowel diseases and blockade of IL-21 in the early phases exacerbates the disease progression in some models of rheumatoid arthritis and systemic lupus erythematosus, thus suggesting a dual role of IL-21 in the control of immune-mediated diseases. IL-21 can exert additional protective functions for the host as it promotes cytotoxic responses against tumors and viruses.
  
  
  CONCLUSIONS
  We here review the available data on the role of IL-21 in chronic inflammatory diseases and discuss the therapeutic benefit of IL-21 inhibitors in such diseases as well as the potential risks of such treatments.
authors.affiliation: University of Rome "Tor Vergata", Department of Systems Medicine , Rome , Italy +39 06 20903702 ; +39 06 72596391 ; Gi.Monteleone@Med.uniroma2.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Di Fusco
authors.forename: Roberta
authors.initials: R
authors.lastname: Izzo
authors.forename: Michele M
authors.initials: MM
authors.lastname: Figliuzzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Pallone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monteleone
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D013601:T-Lymphocytes / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D000893:Anti-Inflammatory Agents; D007378:Interleukins; D000098546:Interleukin-21
keywords: Crohn’s disease; IL-21 receptor; diabetes; psoriasis; rheumatoid arthritis; systemic lupus erythematosus; ulcerative colitis