Molecular and cellular understanding of psoriasis pathogenesis has evolved considerably over the last 30 years beginning in the early 1980s when psoriasis was thought to be a skin disease driven by keratinocyte hyperproliferation. During the next 20 years, the role of the immune system and T-helper (Th) cells in psoriasis pathogenesis was recognized. The presence of the interleukin (IL)-12 cytokine in psoriatic lesions led to the postulate that psoriasis is mediated by Th1 cells. Recent evidence has revealed a role for Th17 cells, and other immune cells, as proximal regulators of psoriatic skin inflammation. IL-17A, the principal effector cytokine of Th17 cells, stimulates keratinocytes to produce chemokines, cytokines, and other proinflammatory mediators thereby enabling IL-17A to bridge the innate and adaptive immune systems to sustain chronic inflammation. This model underlies the rationale for inhibiting IL-17A signaling as a potential therapeutic approach to disrupt the psoriatic inflammatory loop. Several monoclonal antibodies that inhibit the IL-17 pathway are in clinical development. These agents exhibit promising clinical efficacy and tolerability profiles including immunohistochemical improvement in psoriatic plaques. Results from clinical trials with IL-17 pathway inhibitors are refining our understanding of psoriasis pathogenesis and may provide a new therapeutic approach for patients with moderate to severe psoriasis.Le texte complet de cet article est disponible en PDF.
Key words : cytokines, interleukin-17A, interleukin-23, keratinocytes, pathogenesis, psoriasis, T-helper 1 cells, T-helper 17 cells
Abbreviations used : IL, PASI, Th, TNF
| Supported by Novartis Pharmaceuticals Canada Inc.
| Disclosure: Dr Lynde was a consultant, speaker, and advisory board member for Amgen, Pfizer, AbbVie, Janssen, Novartis, and Celgene, and was an investigator for Amgen, Pfizer, AbbVie, Janssen, Lilly, Novartis, and Celgene. Dr Poulin was a speaker and advisory board member for AbbVie, Amgen, and Janssen, and was an investigator for AbbVie, Amgen, Celgene, Centocor, Lilly, Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, and Roche. Dr Vender was a speaker for AbbVie, Amgen, Celgene, Galderma, Janssen, Leo Pharma, Novartis, and Pfizer, and was an investigator for AbbVie, Amgen, Celgene, Galderma, Janssen, Leo Pharma, Novartis, Pfizer, Lilly, and Merck. Dr Bourcier was an advisory board member and speaker for AbbVie, Amgen, Leo Pharma, and Janssen; a speaker for Astellas and Merck; and an investigator for AbbVie, Astellas, Amgen, Leo Pharma, Novartis, Janssen, Lilly, Pfizer, and Celgene. Dr Khalil is an employee of Novartis.
| Reprints not available from the authors.