T cell-independent mechanisms associated with neutrophil extracellular trap formation and selective autophagy in IL-17A-mediated epidermal hyperplasia

Erika Suzuki, Emanual Michael Maverakis, Ritu Sarin, Laura Bouchareychas, Vijay K. Kuchroo, Frank O. Nestle, Iannis Adamopoulos

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

IL-17A has been strongly associated with epidermal hyperplasia in many cutaneous disorders. However, because IL-17A is mainly produced by ab and ≥mma;δT 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 Tcrd-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.

Original languageEnglish (US)
Pages (from-to)4403-4412
Number of pages10
JournalJournal of Immunology
Volume197
Issue number11
DOIs
StatePublished - Dec 1 2016

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ASJC Scopus subject areas

  • Immunology

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