Identification of IL-17F/frequent exacerbator endotype in asthma

Ricciardolo, Fabio Luigi Massimo; Sorbello, Valentina; Folino, Anna; Gallo, Fabio; Massaglia, G M; Favatà, Gabriella; Conticello, S; Vallese, Davide; Gani, Federica; Malerba, Mario; Folkerts, Gert; Rolla, Giovanni; Profita, Mirella; Mauad, Thaís; Stefano, Antonino Di; Ciprandi, Giorgio

doi:10.1016/j.jaci.2016.10.034

Cited by 130 publications

(103 citation statements)

References 49 publications

(68 reference statements)

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“…36 Elevated levels are associated with airway inflammation in mouse models and humans. 37–39 The data from the WTC-exposed FDNY cohort is consistent with a Th-2 and Th-17 response predicting airway remodeling and reactivity. These data support further investigation of the innate Th-17 response to pulmonary irritants.…”

Section: Discussionmentioning

confidence: 54%

Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure

Singh

Liu

Putman

et al. 2018

Chest

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Section: Discussionmentioning

confidence: 54%

Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure

Singh

Liu

Putman

et al. 2018

Chest

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“…Moreover, our study may also be relevant to exacerbations of lung diseases, such as asthma. Higher numbers of neutrophils and Th17 cytokines were recently reported in the bronchial/nasal mucosa of severe asthmatics compared to mild asthmatics, and particularly in severe asthmatics who suffer frequent exacerbations 43, 44 . The presence of endotoxin in house dust in urban environments has been associated with asthma symptoms, use of asthma medications and wheezing 45 .…”

Section: Discussionmentioning

confidence: 92%

Pathogenic TH17 inflammation is sustained in the lungs by conventional dendritic cells and Toll-like receptor 4 signaling

Shalaby

Lyons-Cohen

Whitehead

et al. 2018

Journal of Allergy and Clinical Immunology

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Background Mechanisms that elicit mucosal Th17 cell responses have been described, yet how these cells are sustained in chronically inflamed tissues remains unclear. Objective We sought to understand whether the maintenance of lung Th17 inflammation requires environmental agents in addition to antigen, and to identify the lung antigen-presenting cell types (APCs) that sustain the self-renewal of Th17 cells. Methods Animals were repeatedly exposed to aspiration of ovalbumin alone, or together with environmental adjuvants, including extracts of common house dust (HDE), to test their role in maintaining lung inflammation. Alternatively, antigen-specific effector/memory Th17 cells, generated in culture using CD4+ T cells from Il17a fate-mapping mice, were adoptively transferred to assess their persistence in genetically modified animals lacking distinct lung APC subsets or cell-specific TLR4 signaling. Th17 cells were also co-cultured with lung APC subsets to determine which of these could revive their expansion and activation. Results Th17 cells and consequent neutrophilic inflammation were poorly sustained by inhaled antigen alone, but were augmented by inhalation of antigen together with HDE. This was associated with weight loss and changes in lung physiology consistent with interstitial lung disease. The effect of HDE required TLR4 signaling predominantly in lung hematopoietic cells, including CD11c+ cells. CD103+ and CD11b+ conventional dendritic cells (cDCs) directly interacted with Th17 cells in situ and revived the clonal expansion of Th17 cells ex vivo and in vivo, whereas lung macrophages and B cells could not. Conclusion Th17-dependent inflammation in the lungs can be sustained by persistent TLR4-mediated activation of lung cDCs.

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“…It has been reported that the levels of IL‐17A and IL‐17F in sputum are elevated in patients with asthma and that increased levels of IL‐17A are associated with neutrophilic inflammation, increased AHR, and steroid resistance . Ricciardolo et al . have reported that IL‐17F‐expressing cells are abundant in bronchus in severe asthma with frequent exacerbation.…”

Section: Role Of Th17 Cells In Allergic Airway Inflammationmentioning

confidence: 99%

Allergic airway inflammation: key players beyond the Th2 cell pathway

Hirose

Iwata

Tamachi

et al. 2017

Immunological Reviews

115

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Allergic asthma is characterized by eosinophilic airway inflammation, mucus hyperproduction, and airway hyperreactivity, causing reversible airway obstruction. Accumulating evidence indicates that antigen-specific Th2 cells and their cytokines such as IL-4, IL-5, and IL-13 orchestrate these pathognomonic features of asthma. However, over the past decade, the understanding of asthma pathogenesis has made a significant shift from a Th2 cell-dependent, IgE-mediated disease to a more complicated heterogeneous disease. Recent studies clearly show that not only Th2 cytokines but also other T cell-related cytokines such as IL-17A and IL-22 as well as epithelial cell cytokines such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) are involved in the pathogenesis of asthma. In this review, we focus on the roles of these players beyond Th2 pathways in the pathogenesis of asthma.

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Identification of IL-17F/frequent exacerbator endotype in asthma

Abstract: IL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation, suggesting a pathogenic role of IL-17F in FEs.

Cited by 130 publications

References 49 publications

Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure

Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure

Pathogenic TH17 inflammation is sustained in the lungs by conventional dendritic cells and Toll-like receptor 4 signaling

Allergic airway inflammation: key players beyond the Th2 cell pathway

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