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Interleukin-17 Inhibition for the Treatment of Inflammatory Skin Disease

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Biologic and Systemic Agents in Dermatology

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Abstract

Psoriasis is a chronic inflammatory skin condition characterized by thick, erythematous, scaly plaques. While the etiology of this skin condition has not been fully elucidated, research has unequivocally shown that psoriasis represents a bona fide T cell-mediated disease. The recent discovery of a set of pathogenic T cells that produce high levels of interleukin-17 in response to interleukin-23 led to a major paradigm shift in the pathogenic model for this condition. The astonishing phase III clinical trial results for three novel monoclonal antibodies against interleukin-17 (secukinumab, ixekizumab, and brodalumab) underscore the central role of this cytokine as the predominant driver of psoriatic disease. The role of interleukin-17 blockade for the treatment of other inflammatory skin conditions is not entirely clear, though early studies suggest that this class of medications represents a promising treatment strategy for several noninfectious lymphocytic and neutrophilic dermatoses, such as Sweet syndrome, Behçet disease, and atopic dermatitis.

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Abbreviations

ACR:

American College of Rheumatology

AD:

Atopic dermatitis

ADAMTSL5:

A disintegrin-like and metalloprotease domain containing thrombospondin type 1 motif-like 5

AMPs:

Antimicrobial peptides

C/EBP:

CCAAT-enhancer-binding protein

DLE:

Discoid lupus erythematosus

EAE:

Experimental autoimmune encephalomyelitis

IBD:

Inflammatory bowel disease

IL:

Interleukin

ILC:

Innate lymphoid cells

PASI:

Psoriasis Area and Severity Index

SCLE:

Subacute cutaneous lupus erythematosus

SLE:

Systemic lupus erythematosus

STAT1:

Signal transducer and activator of transcription 1

T17:

Interleukin-17-producing T cells

Tc17:

Interleukin-17-producing CD8+ T cells

Th:

T helper

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Acknowledgments

JEH, JAG, and JGK are supported in part by grant # UL1TR001866 and # KL2TR001865 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program.

Conflict of Interest

JEH and JAG declare that they have no conflict of interest. JGK has been a consultant to and has received research support from companies that have developed or are developing therapeutics for psoriasis: AbbVie, Amgen, Boehringer, Bristol-Myers Squibb, Celgene, Dermira, Idera, Janssen, Leo, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, Serono, Sun, Valeant, and Vitae.

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  1. Jason E. Hawkes and Jose A. Gonzalez contributed equally to this work.

Authors and Affiliations

  1. The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, 10065, USA

    Jason E. Hawkes MD, Jose A. Gonzalez BS & James G. Krueger MD, PhD

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  1. Jason E. Hawkes MD
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  2. Jose A. Gonzalez BS
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  3. James G. Krueger MD, PhD
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Correspondence to James G. Krueger MD, PhD .

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Editors and Affiliations

  1. Division of Dermatology, David Geffen School of Medicine a UCLA, Los Angeles, California, USA

    Paul S. Yamauchi

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Hawkes, J.E., Gonzalez, J.A., Krueger, J.G. (2018). Interleukin-17 Inhibition for the Treatment of Inflammatory Skin Disease. In: Yamauchi, P. (eds) Biologic and Systemic Agents in Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-66884-0_15

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  • DOI: https://doi.org/10.1007/978-3-319-66884-0_15

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