Interleukin 17A: Toward a new understanding of psoriasis pathogenesis

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...

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Bibliographic Details
Published in:Journal of the American Academy of Dermatology 2014-07, Vol.71 (1), p.141-150
Main Authors: Lynde, Charles W., MD, FRCPC, Poulin, Yves, MD, FRCPC, Vender, Ronald, MD, FRCPC, Bourcier, Marc, MD, Khalil, Sam, PhD
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - therapeutic use
cytokines
Dendritic Cells - immunology
Dermatology
History, 20th Century
History, 21st Century
Humans
Immunohistochemistry
Interleukin-17 - antagonists & inhibitors
Interleukin-17 - immunology
interleukin-17A
interleukin-23
keratinocytes
Models, Immunological
pathogenesis
psoriasis
Psoriasis - drug therapy
Psoriasis - history
Psoriasis - immunology
Psoriasis - metabolism
T-helper 17 cells
T-helper 1 cells
Th17 Cells - drug effects
Th17 Cells - immunology
Tumor Necrosis Factor-alpha - antagonists & inhibitors
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Summary: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.
ISSN:0190-9622
1097-6787
DOI:10.1016/j.jaad.2013.12.036