title: T Cell-Independent Mechanisms Associated with Neutrophil Extracellular Trap Formation and Selective Autophagy in IL-17A-Mediated Epidermal Hyperplasia.
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-1hicells, 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.
authors: Division of Rheumatology, Allergy and Clinical Immunology, Department of Internal Medicine, University of California at Davis, Davis, CA 95616.
authors: Erika
authors: E
authors: Suzuki
authors: Department of Dermatology, University of California at Davis, Davis, CA 95616.
authors: Emanual
authors: E
authors: Maverakis
authors: Division of Rheumatology, Allergy and Clinical Immunology, Department of Internal Medicine, University of California at Davis, Davis, CA 95616.
authors: Ritu
authors: R
authors: Sarin
authors: Division of Rheumatology, Allergy and Clinical Immunology, Department of Internal Medicine, University of California at Davis, Davis, CA 95616.
authors: Laura
authors: L
authors: Bouchareychas
authors: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors: Vijay K
authors: VK
authors: Kuchroo
authors: Division of Genetics and Molecular Medicine, St. John's Institute of Dermatology, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, United Kingdom; and.
authors: Frank O
authors: FO
authors: Nestle
authors: Division of Rheumatology, Allergy and Clinical Immunology, Department of Internal Medicine, University of California at Davis, Davis, CA 95616; iannis@ucdavis.edu.|Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, CA 95817.
authors: Iannis E
authors: IE
authors: Adamopoulos
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000276:immunology*; D004848:Epithelium / Q000276:immunology* / Q000473:pathology; D065206:Extracellular Traps / Q000235:genetics / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006965:Hyperplasia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D018398:Homeodomain Proteins; C098680:Il17a protein, mouse; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; C528688:interleukin-23 receptor, mouse; C064658:RAG-1 protein