Th17 cells and IL-17 A—Focus on immunopathogenesis and immunotherapeutics

van den Berg, W.B. and McInnes, I.B. (2013) Th17 cells and IL-17 A—Focus on immunopathogenesis and immunotherapeutics. Seminars in Arthritis and Rheumatism, 43(2), pp. 158-170. (doi:10.1016/j.semarthrit.2013.04.006) (PMID:24157091)

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Abstract

Importance: 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.

Objectives: 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.

Conclusion: Targeting the IL-17 pathway shows promise as strategy to treat immune-mediated diseases ranging from skin to joints.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain
Authors: van den Berg, W.B., and McInnes, I.B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Seminars in Arthritis and Rheumatism
ISSN:0049-0172
ISSN (Online):1532-866X

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