IL-17A and Th17 cells as therapeutic targets for autoimmune diseases
The definition of the CD3+ CD4+ Th17 cell subset and the identification of the IL-23-Th17 axis have introduced new paradigms to explain the origin of autoimmune events in animal models, subverting the established Th1-Th2 paradigm. IL-17A has been pivotal for the discovery of the Th17 lineage, which probably evolved as an arm of the adaptive immune system for host protection against extracellular bacteria and fungi. IL-17A, is the founding member of the IL-17 family composed of six members. Th17 cells and IL-17A have been implicated in a variety of inflammatory and autoimmune diseases in rodents. In these models, Th17 cells are pivotal in the pathogenesis of the disease and IL-17A appears to be the main mediator, but the situation might be different in humans. In some human pathological conditions, in addition to Th17 cells, other IL-17A-producing cells have been described, including CD8+ T cells, astrocytes, macrophages and Langerhans cells. The therapeutic effect of some new biologics can now, at least in part, be explained by their interference with mediators involved in the generation of Th17 cells, but more specific treatments would be valuable to dissect these intricate networks. An antibody neutralizing IL-17A is being evaluated under different autoimmune conditions. This approach might not only benefit patients, but, by neutralizing IL-17A selectively, might also help to define the role of this cytokine in autoimmune disorders and contribute to a new wave of selective and targeted therapies.
KeywordsTh17 Cell Juvenile Idiopathic Arthritis Th17 Cell Subset Chronic Active Lesion Ankylose Spondilitis
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- 14.McAllister F, Henry A, Kreindler JL, Dubin PJ, Ulrich L, Steele C, Finder JD, Pilewski JM, Carreno BM, Goldman SJ et al (2005) Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-a and granulocyte colony-stimulating factor in bronchial epithelium: Implications for airway inflammation in cystic fibrosis. J Immunol 175: 404–412PubMedGoogle Scholar
- 52.Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, Dooley LT, Gordon KB (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 371: 1665–1674PubMedCrossRefGoogle Scholar
- 53.Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, Guzzo C, Hsu MC, Wang Y, Li S et al (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 371: 1675–1684PubMedCrossRefGoogle Scholar