Eosinophil extracellular traps activate type 2 innate lymphoid cells through stimulating airway epithelium in severe asthma

Background Activated eosinophils release extracellular traps (EETs), which contribute to airway inflammation in severe asthma (SA). However, the role of EETs in innate immunity has not yet been completely determined. The present study aimed to demonstrate the mechanism of airway inflammation in SA m...

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Vydáno v:Allergy (Copenhagen) Ročník 75; číslo 1; s. 95 - 103
Hlavní autoři: Choi, Youngwoo, Kim, Young‐Min, Lee, Hee‐Ra, Mun, Jiyeong, Sim, Soyoon, Lee, Dong‐Hyun, Pham, Duy Le, Kim, Seung‐Hyun, Shin, Yoo Seob, Lee, Seung‐Woo, Park, Hae‐Sim
Médium: Journal Article
Jazyk:angličtina
Vydáno: Denmark Blackwell Publishing Ltd 01.01.2020
Témata:
Adult
Aged
Alveoli
Animals
Asthma
Asthma - immunology
Bronchus
eosinophils
Eosinophils - immunology
Epithelium
extracellular traps
Extracellular Traps - immunology
Female
Humans
Immune response
Innate immunity
innate lymphoid cells
Leukocytes (eosinophilic)
Lymphocyte Subsets - immunology
Lymphocytes - immunology
Lymphoid cells
Male
Mice
Mice, Inbred BALB C
Middle Aged
RAG1 protein
Respiratory Mucosa - immunology
Respiratory tract
Respiratory tract diseases
severe asthma
Thymic stromal lymphopoietin
Traps
severe asthma
eosinophils
extracellular traps
epithelium
innate lymphoid cells
ISSN:0105-4538, 1398-9995, 1398-9995
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Shrnutí:Background Activated eosinophils release extracellular traps (EETs), which contribute to airway inflammation in severe asthma (SA). However, the role of EETs in innate immunity has not yet been completely determined. The present study aimed to demonstrate the mechanism of airway inflammation in SA mediated by EETs. Methods Peripheral counts of EET+ eosinophils and type 2 innate lymphoid cells (ILC2s) were evaluated in patients with SA (n = 13), nonsevere asthma (NSA, n = 17), and healthy control subjects (HC, n = 8). To confirm the effect of EETs, airway hyperresponsiveness (AHR) and adapted/innate immune responses were assessed in mice. Furthermore, the effects of anti‐IL‐33/TSLP antibody were tested. Results The numbers of EET+ eosinophils and ILC2s were significantly elevated in SA, with a positive correlation between these two cells (r = .539, P < .001). When mice were injected with EETs, we observed significant increases in epithelium‐derived cytokines (IL‐1α, IL‐1β, CXCL‐1, CCL24, IL‐33, and TSLP) and eosinophil/neutrophil count in bronchoalveolar lavage fluid (BALF) as well as an increased proportion of IL‐5‐ or IL‐13‐producing ILC2s in the lungs. When Rag1−/− mice receiving ILC2s were treated with EETs, increased AHR and IL‐5/IL‐13 levels in BALF were noted, which were effectively suppressed by anti‐IL‐33 or anti‐TSLP antibody. Conclusion EETs could enhance innate and type 2 immune responses in SA, in which epithelium‐targeting biologics (anti‐IL‐33/TSLP antibody) may have a potential benefit. The numbers of EET+ eosinophils and type 2 innate lymphoid cells (ILC2s) are significantly elevated in severe asthma. EETs treatment in mice induces significant increase of epithelium‐derived cytokines (IL‐1α, IL‐1β, CXCL‐1, CCL24, IL‐33, and TSLP) and eosinophil/neutrophil count in bronchoalveolar lavage fluid. EETs activate IL‐5 or IL‐13‐producing ILC2s through stimulating airway epithelium.Abbreviations: EETs, Eosinophil extracellular traps; TSLP, Thymic stromal lymphopoietin
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0105-4538
1398-9995
1398-9995
DOI:10.1111/all.13997