IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation.

Abstract

IL-17E (IL-25) is a member of the IL-17 cytokine family involved in the promotion of type 2 immune responses. Recently, IL-17E has been reported to be up-regulated in distinct skin inflammatory diseases such as psoriasis and atopic and contact dermatitis. We assessed the role played by IL-17E in skin inflammation. Here, we show that IL-17E induces skin inflammation in vivo, characterized by the expression of innate immune response genes and the recruitment of innate immune cells, particularly neutrophils. Genetic deletion or IL-17E neutralization ameliorated skin inflammation induced by imiquimod application or tape stripping, with reductions in neutrophil and macrophage infiltration as assessed by t-distributed stochastic neighbor embedding-guided multiparameter flow cytometry analysis, in mice. In humans, IL-17E promotes the recruitment of neutrophils via activation of macrophages in a p38-dependent mechanism. In addition, IL-17E is up-regulated in neutrophil-rich inflammatory skin diseases, such as pyoderma gangrenosum and acute generalized exanthematous pustulosis. Our data show a role for IL-17E in skin inflammation that is unrelated to the development of type 2 immune reactions. We propose that IL-17E is an important common denominator of chronic skin inflammation, promoting innate immune cell recruitment and activation.

• Authors: Luisa Senra, Alessio Mylonas, Ruairi D Kavanagh, Padraic G Fallon, Curdin Conrad, Julia Borowczyk-Michalowska, Ludovic Jean Wrobel, Guerkan Kaya, Nikhil Yawalkar, Wolf-Henning Boehncke, Nicolo Costantino Brembilla
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 139 Issue 8 Pg. 1732-1742.e17 (08 2019) ISSN: 1523-1747 [Electronic] United States
• PMID: 30738055 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• IL25 protein, human
• Interleukin-17
• Interleukins
• Mydgf protein, mouse
• p38 Mitogen-Activated Protein Kinases
• Imiquimod

Topics

• Acute Generalized Exanthematous Pustulosis (immunology, pathology)
• Adjuvants, Immunologic (administration & dosage)
• Animals
• Dermatitis (immunology, pathology)
• Disease Models, Animal
• Female
• Humans
• Imiquimod (administration & dosage)
• Immunity, Innate
• Interleukin-17 (immunology, metabolism)
• Interleukins (genetics, immunology, metabolism)
• Macrophages (immunology, metabolism)
• Mice
• Mice, Knockout
• Neutrophils (immunology, metabolism)
• Pyoderma Gangrenosum (immunology, pathology)
• Skin (cytology, immunology, pathology)
• Up-Regulation
• p38 Mitogen-Activated Protein Kinases (metabolism)