Inmunology Unit, Complejo Asistencial Universitario e Instituto de Biomedicina Universidad de León (IBIOMED), León, Spain
Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies.
Interleukin 17 (IL-17) is a proinflammatory cytokine that has been the focus of intensive research because of its crucial role in the pathogenesis of different diseases across many medical specialties. In this context, the present review in which a panel of 13 experts in immunology, dermatology, rheumatology, neurology, hematology, infectious diseases, hepatology, cardiology, ophthalmology and oncology have been involved, puts in common the mechanisms through which IL-17 is considered a molecular target for the development of novel biological therapies in these different fields. A comprehensive review of the literature and analysis of the most outstanding evidence have provided the basis for discussing the most relevant data related to IL-17A blocking agents for the treatment of different disorders, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, cardiovascular disorders, non alcoholic fatty liver disease, multiple sclerosis, inflammatory bowel disease, uveitis, hematological and solid cancer. Current controversies are presented giving an opening line for future research.
Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland
IL-17 receptor-based signaling and implications for disease.
IL-17 is a highly versatile pro-inflammatory cytokine crucial for a variety of processes, including host defense, tissue repair, the pathogenesis of inflammatory disease and the progression of cancer. In contrast to its profound impact in vivo, IL-17 exhibits surprisingly moderate activity in cell-culture models, which presents a major knowledge gap about the molecular mechanisms of IL-17 signaling. Emerging studies are revealing a new dimension of complexity in the IL-17 pathway that may help explain its potent and diverse in vivo functions. Discoveries of new mRNA stabilizers and receptor-directed mRNA metabolism have provided insights into the means by which IL-17 cooperates functionally with other stimuli in driving inflammation, whether beneficial or destructive. The integration of IL-17 with growth-receptor signaling in specific cell types offers new understanding of the mitogenic effect of IL-17 on tissue repair and cancer. This Review summarizes new developments in IL-17 signaling and their pathophysiological implications.
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