Skin and Systemic Inflammation in Schnitzler's Syndrome Are Associated With Neutrophil Extracellular Trap Formation
Schnitzler's syndrome is a rare autoinflammatory disorder characterized by interleukin-1ß-mediated and neutrophil-dominated inflammation. Neutrophil extracellular traps (NETs) are web-like structures of decondensed chromatin, histones, and antimicrobial peptides released by neutrophils. NETs we...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2019-03-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00546/full |
id |
doaj-334d2a64b53745879ad13a32de2baaa3 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hanna Bonnekoh Hanna Bonnekoh Jörg Scheffel Jörg Scheffel Jim Wu Sheila Hoffmann Marcus Maurer Marcus Maurer Karoline Krause Karoline Krause |
spellingShingle |
Hanna Bonnekoh Hanna Bonnekoh Jörg Scheffel Jörg Scheffel Jim Wu Sheila Hoffmann Marcus Maurer Marcus Maurer Karoline Krause Karoline Krause Skin and Systemic Inflammation in Schnitzler's Syndrome Are Associated With Neutrophil Extracellular Trap Formation Frontiers in Immunology Schnitzler's syndrome neutrophil extracellular traps neutrophils autoinflammation autoimmunity neutrophilic dermatosis |
author_facet |
Hanna Bonnekoh Hanna Bonnekoh Jörg Scheffel Jörg Scheffel Jim Wu Sheila Hoffmann Marcus Maurer Marcus Maurer Karoline Krause Karoline Krause |
author_sort |
Hanna Bonnekoh |
title |
Skin and Systemic Inflammation in Schnitzler's Syndrome Are Associated With Neutrophil Extracellular Trap Formation |
title_short |
Skin and Systemic Inflammation in Schnitzler's Syndrome Are Associated With Neutrophil Extracellular Trap Formation |
title_full |
Skin and Systemic Inflammation in Schnitzler's Syndrome Are Associated With Neutrophil Extracellular Trap Formation |
title_fullStr |
Skin and Systemic Inflammation in Schnitzler's Syndrome Are Associated With Neutrophil Extracellular Trap Formation |
title_full_unstemmed |
Skin and Systemic Inflammation in Schnitzler's Syndrome Are Associated With Neutrophil Extracellular Trap Formation |
title_sort |
skin and systemic inflammation in schnitzler's syndrome are associated with neutrophil extracellular trap formation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-03-01 |
description |
Schnitzler's syndrome is a rare autoinflammatory disorder characterized by interleukin-1ß-mediated and neutrophil-dominated inflammation. Neutrophil extracellular traps (NETs) are web-like structures of decondensed chromatin, histones, and antimicrobial peptides released by neutrophils. NETs were initially described in the context of pathogen defense but are also involved in autoimmune-mediated skin diseases. Here, we assessed the role of neutrophil extracellular trap formation (NETosis) in Schnitzler's syndrome. Immunofluorescence co-staining of myeloperoxidase and subnucleosomal complex was performed on lesional skin samples from patients with Schnitzler's syndrome, other neutrophilic dermatoses (cryopyrin-associated periodic syndrome, Sweet syndrome, and pyoderma gangrenosum), urticarial vasculitis and chronic spontaneous urticaria as well as healthy control skin. Blood neutrophils from patients with Schnitzler's syndrome and controls were isolated, and NETosis was induced by phorbol 12-myristate 13-acetate (PMA). Also, NETosis of control neutrophils induced by symptomatic Schnitzler's syndrome sera, cytokines and sub-threshold PMA doses was studied. Immunofluorescence co-staining revealed widespread and substantial NET formation in lesional skin of Schnitzler's syndrome patients but absence of NETs in chronic spontaneous urticaria and control skin. Neutrophils undergoing NETosis were observed in the skin of other neutrophilic diseases too. Correspondingly, blood neutrophils from Schnitzler's syndrome patients showed significantly elevated NETosis rates compared to control neutrophils following stimulation with PMA. Increased NETosis correlated well with high levels of C-reactive protein (CRP). SchS patients with the lowest NETosis rates had persistent joint and bone pain despite IL-1 blockade. Stimulation of control neutrophils and sub-threshold PMA with sera of symptomatic Schnitzler's syndrome patients disclosed enhanced NETosis as compared to control sera. Our results suggest that the induction of NET formation by neutrophils contributes to skin and systemic inflammation and may support the resolution of local inflammation in Schnitzler's syndrome. |
topic |
Schnitzler's syndrome neutrophil extracellular traps neutrophils autoinflammation autoimmunity neutrophilic dermatosis |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.00546/full |
work_keys_str_mv |
AT hannabonnekoh skinandsystemicinflammationinschnitzlerssyndromeareassociatedwithneutrophilextracellulartrapformation AT hannabonnekoh skinandsystemicinflammationinschnitzlerssyndromeareassociatedwithneutrophilextracellulartrapformation AT jorgscheffel skinandsystemicinflammationinschnitzlerssyndromeareassociatedwithneutrophilextracellulartrapformation AT jorgscheffel skinandsystemicinflammationinschnitzlerssyndromeareassociatedwithneutrophilextracellulartrapformation AT jimwu skinandsystemicinflammationinschnitzlerssyndromeareassociatedwithneutrophilextracellulartrapformation AT sheilahoffmann skinandsystemicinflammationinschnitzlerssyndromeareassociatedwithneutrophilextracellulartrapformation AT marcusmaurer skinandsystemicinflammationinschnitzlerssyndromeareassociatedwithneutrophilextracellulartrapformation AT marcusmaurer skinandsystemicinflammationinschnitzlerssyndromeareassociatedwithneutrophilextracellulartrapformation AT karolinekrause skinandsystemicinflammationinschnitzlerssyndromeareassociatedwithneutrophilextracellulartrapformation AT karolinekrause skinandsystemicinflammationinschnitzlerssyndromeareassociatedwithneutrophilextracellulartrapformation |
_version_ |
1725121920978911232 |
spelling |
doaj-334d2a64b53745879ad13a32de2baaa32020-11-25T01:23:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00546436948Skin and Systemic Inflammation in Schnitzler's Syndrome Are Associated With Neutrophil Extracellular Trap FormationHanna Bonnekoh0Hanna Bonnekoh1Jörg Scheffel2Jörg Scheffel3Jim Wu4Sheila Hoffmann5Marcus Maurer6Marcus Maurer7Karoline Krause8Karoline Krause9Department of Dermatology and Allergy, Allergie-Centrum-Charité, Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyAutoinflammation Reference Center Charité (ARC2), Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyDepartment of Dermatology and Allergy, Allergie-Centrum-Charité, Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyAutoinflammation Reference Center Charité (ARC2), Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyDepartment of Dermatology and Allergy, Allergie-Centrum-Charité, Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyGerman Center for Neurodegenerative Diseases, Berlin, GermanyDepartment of Dermatology and Allergy, Allergie-Centrum-Charité, Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyAutoinflammation Reference Center Charité (ARC2), Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyDepartment of Dermatology and Allergy, Allergie-Centrum-Charité, Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyAutoinflammation Reference Center Charité (ARC2), Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanySchnitzler's syndrome is a rare autoinflammatory disorder characterized by interleukin-1ß-mediated and neutrophil-dominated inflammation. Neutrophil extracellular traps (NETs) are web-like structures of decondensed chromatin, histones, and antimicrobial peptides released by neutrophils. NETs were initially described in the context of pathogen defense but are also involved in autoimmune-mediated skin diseases. Here, we assessed the role of neutrophil extracellular trap formation (NETosis) in Schnitzler's syndrome. Immunofluorescence co-staining of myeloperoxidase and subnucleosomal complex was performed on lesional skin samples from patients with Schnitzler's syndrome, other neutrophilic dermatoses (cryopyrin-associated periodic syndrome, Sweet syndrome, and pyoderma gangrenosum), urticarial vasculitis and chronic spontaneous urticaria as well as healthy control skin. Blood neutrophils from patients with Schnitzler's syndrome and controls were isolated, and NETosis was induced by phorbol 12-myristate 13-acetate (PMA). Also, NETosis of control neutrophils induced by symptomatic Schnitzler's syndrome sera, cytokines and sub-threshold PMA doses was studied. Immunofluorescence co-staining revealed widespread and substantial NET formation in lesional skin of Schnitzler's syndrome patients but absence of NETs in chronic spontaneous urticaria and control skin. Neutrophils undergoing NETosis were observed in the skin of other neutrophilic diseases too. Correspondingly, blood neutrophils from Schnitzler's syndrome patients showed significantly elevated NETosis rates compared to control neutrophils following stimulation with PMA. Increased NETosis correlated well with high levels of C-reactive protein (CRP). SchS patients with the lowest NETosis rates had persistent joint and bone pain despite IL-1 blockade. Stimulation of control neutrophils and sub-threshold PMA with sera of symptomatic Schnitzler's syndrome patients disclosed enhanced NETosis as compared to control sera. Our results suggest that the induction of NET formation by neutrophils contributes to skin and systemic inflammation and may support the resolution of local inflammation in Schnitzler's syndrome.https://www.frontiersin.org/article/10.3389/fimmu.2019.00546/fullSchnitzler's syndromeneutrophil extracellular trapsneutrophilsautoinflammationautoimmunityneutrophilic dermatosis |