The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings.
Although the histological changes seen in psoriasis have long been well characterized, the underlying cellular and molecular mechanisms have only begun to be elucidated over the past 20 years. Proinflammatory factors such as tumor necrosis factor (TNF)-α have a central role in psoriasis pathogenesis, and many T-helper 1 (Th1) cytokines and messenger RNAs are elevated in psoriatic lesions. IL-17A, IL-17F, and other Th17 cell-derived cytokines have been shown in murine models to induce features that mimic human psoriasis. This review focuses on the emerging biology of the IL-17 cytokine family in psoriasis, and on the molecular and genetic information gained from animal models and human clinical studies that confirm IL-17 as a crucial proinflammatory cytokine in psoriasis. Expression of IL-17A, IL-17C, and IL-17F is strikingly increased in psoriatic lesions, and successful therapy is associated with restoration of the expression of a wide range of genes (including effector molecules downstream of IL-17 such as cytokines, chemokines, and antimicrobial peptides) to near-normal levels. Therapeutic agents in development that target IL-17 are discussed, and an emerging model of the key role of IL-17 in the pathogenesis of psoriasis is presented.
Medical Sciences, Amgen, Seattle, WA, USA. davidm02@amgen.com
David A
DA
Martin
Jennifer E
JE
Towne
Gregory
G
Kricorian
Paul
P
Klekotka
Johann E
JE
Gudjonsson
James G
JG
Krueger
Chris B
CB
Russell
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003879:Dermatologic Agents / Q000627:therapeutic use; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology*; D059467:Transcriptome / Q000187:drug effects; D016896:Treatment Outcome
D016207:Cytokines; D003879:Dermatologic Agents; D020381:Interleukin-17