Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Sep 26;24(1):231.
doi: 10.1186/s12931-023-02504-4.

Eosinophil extracellular traps in asthma: implications for pathogenesis and therapy

Kunlu Shen  1   2 , Mengyuan Zhang  1   2 , Ruiheng Zhao  1   3 , Yun Li  1   3 , Chunxiao Li  1   4 , Xin Hou  1   4 , Bingqing Sun  1   2 , Bowen Liu  1   3 , Min Xiang  1   3 , Jiangtao Lin  5   6   7   8
Affiliations
Review

Eosinophil extracellular traps in asthma: implications for pathogenesis and therapy

Kunlu Shen et al. Respir Res. .

Abstract

Asthma is a common, chronic inflammatory disease of the airways that affects millions of people worldwide and is associated with significant healthcare costs. Eosinophils, a type of immune cell, play a critical role in the development and progression of asthma. Eosinophil extracellular traps (EETs) are reticular structures composed of DNA, histones, and granulins that eosinophils form and release into the extracellular space as part of the innate immune response. EETs have a protective effect by limiting the migration of pathogens and antimicrobial activity to a controlled range. However, chronic inflammation can lead to the overproduction of EETs, which can trigger and exacerbate allergic asthma. In this review, we examine the role of EETs in asthma.

Keywords: Anti-EETs; Asthma; EETs; Eosinophil extracellular trap cell death; Eosinophil extracellular traps; Therapeutics.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Time course of EETosis. Many ex vivo and in vivo stimuli can lead to human eosinophil activation, increased intracellular Ca2 + and reactive oxygen species production, PAD4-mediated citrullination of nucleosomal histones, resulting in chromatin decondensation with nuclear rounding. Additionally, there is galectin-10 redistribution and occasional formation of intracellular CLCs prior to plasma membrane lysis. Finally, both nuclear and plasma membranes are disassembled, and reticulated chromatin structures are released. EETosis: Eosinophil extracellular trap cell death; PAD4: Peptidyl arginine deaminase 4; CLCs: Charcot-Leyden crystals; EETs: Eosinophil extracellular traps
Fig. 2
Fig. 2
The double-edged sword effect of EETs. EETs are reticular structures composed of DNA, histones, and granulins that are formed by eosinophils and released into the extracellular compartment, forming one of the components of the innate immune response. Components of EETs play an active role in the control of infections by trapping and destroying microorganisms, including viruses, fungi, bacteria, and protozoan pathogens. Although EETs can protect the host from microorganisms, excessive EETs can be harmful to the host. While the early stages of asthma are characterized by an increase in eosinophils, in the severe stage of asthma, activated eosinophils can release excessive amounts of EETs, causing airway epithelial damage and CLC production, making sputum more difficult to cough up, in addition to exacerbating the type 2 inflammatory response by interacting with other immune cells. T2: Type 2; CS: Corticosteroids; EETs: Eosinophil extracellular traps; ECP: Eosinophil cationic protein; MBP: Major basic protein; EDN: Eosinophil-derived neurotoxin; EPO: Eosinophil peroxidase; CLCs: Charcot-Leyden crystals
Fig. 3
Fig. 3
Therapeutic potential drugs targeting a step in the release and formation of EETs. Many stimuli can induce eosinophil activation and the release of EETs, so therapeutic strategies for EETs need to be evaluated and selected on an individual basis. E.coli: Escherichia coli; RSV: Respiratory Syncytial Virus; PMA: Phorbol 12-myristate 13-acetate; LPS: lipopolysaccharide; C5a: Complement factor 5a; Ig: Immunoglobulin; TSLP: Thymic stromal lymphopoietin; IL-5: Interleukin 5; NADPH: Nicotinamide adenine dinucleotide phosphate; PAD4: Peptidyl arginine deaminase 4; ROS: Reactive oxygen species; DNaseI: Deoxyribonuclease I; CLCs: Charcot-Leyden crystals
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Hammad H, Lambrecht BN. The basic immunology of asthma. Cell. 2021;184(9):2521–2. - PubMed
    1. Ray A, Kolls JK. Neutrophilic inflammation in Asthma and Association with Disease Severity. Trends Immunol. 2017;38(12):942–54. - PMC - PubMed
    1. Thiam HR, Wong SL, Wagner DD, Waterman CM. Cellular Mechanisms of NETosis. Annu Rev Cell Dev Biol. 2020;36:191–218. - PMC - PubMed
    1. Dl P, Gy B, Sh K, Ys S, Ym Y, Yj C et al. Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology [Internet]. 2017 Jan [cited 2022 Jan 5];47(1). Available from: https://pubmed.ncbi.nlm.nih.gov/27883241/. - PubMed
    1. King-Biggs MB, Asthma Ann Intern Med. 2019;171(7):ITC49–64. - PubMed