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T Cell–Independent Mechanisms Associated with Neutrophil Extracellular Trap Formation and Selective Autophagy in IL-17A–Mediated Epidermal Hyperplasia

Year: 2016
Type: article
Abstract: IL-17A has been strongly associated with epidermal hyperplasia in many cutaneous disorders. However, because IL-17A is mainly produced by αβ and γδT cells in response to IL-23, the role of T cells and IL-23 has overshadowed any IL-17A–independent actions. In this article, we report that IL-17A gene transfer induces epidermal hyperplasia in Il23r−/−Rag1−/−- and Tcrδ-deficient mice, which can be prevented by neutrophil depletion. Moreover, adoptive transfer of CD11b+Gr-1hi cells, after IL-17A gene transfer, was sufficient to phenocopy the disease. We further show that the IL-17A–induced pathology was prevented in transgenic mice with impaired neutrophil extracellular trap formation and/or neutrophils with conditional deletion of the master regulator of selective autophagy, Wdfy3. Our data demonstrate a novel T cell–independent mechanism that is associated with neutrophil extracellular trap formation and selective autophagy in IL-17A–mediated epidermal hyperplasia.
DOI: 10.4049/jimmunol.1600383
Authors: Erika Suzuki, Emanual Maverakis, Ritu Sarin, Laura Bouchareychas, Vijay K Kuchroo, Frank O Nestle, Iannis E Adamopoulos
Institutions: University of California, Davis, Brigham and Women's Hospital, Harvard University, Guy's Hospital, King's College London, Shriners Hospitals for Children - Northern California
Language: English
Subfield: Immunology
Open Access status: green
Funders: National Psoriasis Foundation, Shriners Hospitals for Children, National Institutes of Health, University of California, Davis, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases
OpenAlex ID: W2543632126
FWCI: 2.429
Cites: 40
Cited by: 43
Related to: 10