IL-17F, rather than IL-17A, underlies airway inflammation in a steroid-insensitive toluene diisocyanate-induced asthma model

Chen, Rongchang; Zhang, Qingling; Chen, Shuyu; Tang, Haixiong; Huang, Peikai; Wei, Shushan; Liang, Zhenyu; Chen, Xin; Tao, Ailin; Yao, Le

doi:10.1183/13993003.01510-2018

Cited by 31 publications

(18 citation statements)

References 39 publications

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“…IL-17A and IL17F bind to receptor complexes, with IL-17RA serving as the common subunit. Nevertheless, a recent study with mice models suggested that IL-17F, rather than IL-17A, underlies airway inflammation in steroid-insensitive asthma [ 103 ].…”

Section: Future Therapeutic Targetsmentioning

confidence: 99%

Identification and treatment of T2-low asthma in the era of biologics

et al. 2020

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Currently, and based on the development of relevant biologic therapies, T2-high is the most well-defined endotype of asthma. Although much progress has been made in elucidating T2-high inflammation pathways, no specific clinically applicable biomarkers for T2-low asthma have been identified. The therapeutic approach of T2-low asthma is a problem urgently needing solution, firstly because these patients have poor response to steroids, and secondly because they are not candidates for the newer targeted biologic agents. There is, thus, an unmet need for the identification of biomarkers that can help the diagnosis and endotyping of T2-low asthmaOngoing investigation is focusing on neutrophilic airway inflammation mediators as therapeutic targets, including IL-8, IL-17, IL-1, IL-6, IL-23, TNF-a; molecules that target to restore corticosteroid sensitivity, mainly mitogen-activated protein kinase inhibitors, tyrosine kinase inhibitors and phosphatidylinositol 3-kinase inhibitors; PDE3 inhibitors that act as bronchodilators and PDE4 inhibitors that have an anti-inflammatory effect; and airway smooth muscle mass attenuation therapies, mainly for patients with paucigranulocytic inflammationThis manuscript aims to review the evidence for non-eosinophilic inflammation being a target for therapy in asthma, discuss current and potential future therapeutic approaches, such as novel molecules and biologic agents, and assess clinical trials of licensed drugs in the treatment of T2-low asthma.

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Section: Future Therapeutic Targetsmentioning

confidence: 99%

Identification and treatment of T2-low asthma in the era of biologics

et al. 2020

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“…On the one hand, the disparities in the lung structural changes after long-term cigaretet smoke exposure, between mice deficient with Il17a in a literature 2 , 14 and those dually deficient of Il17a and Il17f in the present study, are likely to be explained by overlapping functions between IL-17A and IL-17F 3 , 4 , 22 . On the other hand, IL-17A is associated with frequent acute exacerbations 10 , 23 , 24 , whereas IL-17F has been linked to lung cancer 25 , and asthma 26 , 27 suggesting that IL-17A and F may have multiple, but indipendent roles in airway pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Dual interleukin-17A/F deficiency protects against acute and chronic response to cigarette smoke exposure in mice

Wada

Nakamura

Inoue

et al. 2021

Sci Rep

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IL-17A and IL-17F are both involved in the pathogenesis of neutrophilic inflammation observed in COPD and severe asthma. To explore this, mice deficient in both Il17a and Il17f and wild type (WT) mice were exposed to cigarette smoke or environmental air for 5 to 28 days and changes in inflammatory cells in bronchoalveolar lavage (BAL) fluid were determined. We also measured the mRNA expression of keratinocyte derived chemokine (Kc), macrophage inflammatory protein-2 (Mip2), granulocyte–macrophage colony stimulating factor (Gmcsf) and matrix metalloproteinase-9 (Mmp9 ) in lung tissue after 8 days, and lung morphometric changes after 24 weeks of exposure to cigarette smoke compared to air-exposed control animals. Macrophage counts in BAL fluid initially peaked at day 8 and again on day 28, while neutrophil counts peaked between day 8 and 12 in WT mice. Mice dual deficient with Il17a and 1l17f showed similar kinetics with macrophages and neutrophils, but cell numbers at day 8 and mRNA expression of Kc, Gmcsf and Mmp9 were significantly reduced. Furthermore, airspaces in WT mice became larger after cigarette smoke exposure for 24 weeks, whereas this was not seen dual Il17a and 1l17f deficient mice. Combined Il17a and Il17f deficiency resulted in significant attenuation of neutrophilic inflammatory response and protection against structural lung changes after long term cigarette smoke exposure compared with WT mice. Dual IL-17A/F signalling plays an important role in pro-inflammatory responses associated with histological changes induced by cigarette smoke exposure.

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“…Studies on the pathogenesis of TDI OA have shown that both eosinophilic (high type 2 airway inflammation) and non-eosinophilic (low type 2 airway inflammation) mechanisms are important [11]. The pathogenesis of TDI-induced asthma in at least one mouse model depends on the Th17 response: IL-17A suppresses TH2 inflammation with eosinophil recruitment, whereas IL17F drives Th17 inflammation and neutrophil increase in airways [19].…”

Section: Discussionmentioning

confidence: 99%

Asthma Case Cluster during Renovation of a Water-Damaged and Toxic Building

Hyvönen¹,

Syrjälä

2019

Microorganisms

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Background: An association between fungal exposure at work and asthma onset has been shown, but a causal relationship between them has not beTanle en established. Methods: The study describes an asthma cluster in workers in a building under renovation. Before renovation the work site had significant water damage, technical deficiencies, and ventilation problems. Worker protection was insufficient during renovation. In the building, toxicity was determined from dust as well as from cultured dust. Toxicity analysis was conducted in vitro using the boar spermatozoa motility assay. Results: During the 8-month renovation period, among 290 workers, 21 (7.2%) experienced new-onset asthma (9 women, 42.9%; 12 men, 57.1%; median age, 43 years (range, 30–60 years)). At the renovation site, they had been exposed to areas where remarkable toxicity was demonstrated in vitro. One year later, 13 (61.9%) of them still had moderate disease, and three (14.8%) had severe disease. Most patients had a poor response to inhaled corticosteroids. Conclusions: This study documents a clear temporal association between occupational exposure during renovation of a water-damaged building and a cluster of 21 new occupational asthma cases. In addition, dust and cultured dust from their work spaces showed remarkable toxicity based on inhibition of boar sperm motility in vitro.

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IL-17F, rather than IL-17A, underlies airway inflammation in a steroid-insensitive toluene diisocyanate-induced asthma model

Cited by 31 publications

References 39 publications

Identification and treatment of T2-low asthma in the era of biologics

Identification and treatment of T2-low asthma in the era of biologics

Dual interleukin-17A/F deficiency protects against acute and chronic response to cigarette smoke exposure in mice

Asthma Case Cluster during Renovation of a Water-Damaged and Toxic Building

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