title: Th17 cells and IL-17 a--focus on immunopathogenesis and immunotherapeutics.
abstract: OBJECTIVE
  Accumulating evidence suggests that IL-17 A has broad pathogenic roles in multiple autoimmune and immune-mediated inflammatory diseases, including psoriasis and rheumatoid arthritis (RA). The development of new therapies that inhibit IL-17 pathway signaling is of clinical significance.
  
  
  OBJECTIVE
  This review aims to summarize the current preclinical evidence on the role of Th17 cells and IL-17 and related cytokines in immune-mediated disease pathophysiology, with a focus on psoriasis and rheumatoid arthritis, as well as to summarize recent clinical trials in these indications with newly developed IL-17 pathway inhibitors.
  
  
  METHODS
  A systematic literature search was conducted of PubMed using relevant keywords. Studies were assessed according to recent relevance to IL-17-mediated pathophysiology and clinical IL-17 inhibition. Experimental animal models of autoimmune disease and clinical studies that focused on IL-17 pathway inhibitors were included.
  
  
  RESULTS
  Preclinical studies suggest that IL-17A is an attractive therapeutic target. Several IL-17A inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibodies, secukinumab and ixekizumab, and the anti-17RA monoclonal antibody brodalumab. Each has shown variable and sometimes favorable results in proof-of-concept and phase II clinical trials and is currently undergoing further clinical evaluation in a range of immune-mediated diseases.
  
  
  CONCLUSIONS
  Targeting the IL-17 pathway shows promise as strategy to treat immune-mediated diseases ranging from skin to joints.
authors.affiliation: Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands. Electronic address: w.vandenberg@reuma.umcn.nl.
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D020381:Interleukin-17
keywords: Brodalumab; Interleukin-17; Ixekizumab; Secukinumab; Th17 cells