Increased serum IL-17 is an independent risk factor for severe asthma

Agache, Ioana; Ciobanu, Cristina; Agache, Costel; Anghel, Mariana

doi:10.1016/j.rmed.2010.02.018

Cited by 223 publications

(200 citation statements)

References 15 publications

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“…Moreover, although allergic asthma is mainly a Th2-related disease, recent studies have shown that the Th17 cell, a newly identified effector T cell, may also contribute to allergic inflammation. 108,109 DCs are important for Th17 cell development, but the role of post-infection DCs in modulating allergic Th17 responses has not been addressed. Further investigation into the mechanisms by which DCs are 'educated' by infection at different stages of host development will enhance the understanding of immune regulation in disease settings and will be useful in the rational design of preventive/therapeutic approaches to allergy/asthma and infections.…”

Section: Discussionmentioning

confidence: 99%

Role of dendritic cells: a step forward for the hygiene hypothesis

Yang

Gao

2010

Cell Mol Immunol

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The hygiene hypothesis was proposed more than two decades ago, but its mechanism remains unclear. This review focuses on recent advances in the field, especially on the role played by dendritic cells (DCs) and their modulating effects on various infections and allergic diseases, including allergic asthma. DCs isolated from mice long after the resolution of an infection were reported to have a significant modulating effect on allergen-specific Th2 responses in both in vitro and in vivo systems. These DCs showed DC1-like and/or tolerogenic DC capacity, which allowed for the inhibition of allergic responses by immune deviation (enhancing Th1 response) and immune regulation (through regulatory T-cell and Th2 hyporesponsiveness) mechanisms. These findings represented a significant advance in the elucidation of the mechanisms underlying the hygiene hypothesis. Further investigation on the mechanisms by which DCs are 'educated' by infectious agents and the influence of the type, time, and extent of infections on this 'education' process will help us understand immune regulation in disease settings and in the rational design of preventive/therapeutic approaches to allergy/asthma and infections.

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Section: Discussionmentioning

confidence: 99%

Role of dendritic cells: a step forward for the hygiene hypothesis

Yang

Gao

2010

Cell Mol Immunol

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“…In this study, however, patients with or without atopy were not consistently separated in the analysis. The most interesting finding by AGACHE et al [44] was that a serum IL-17A concentration exceeding a threshold (20 pg?mL -1 ) is associated with a more than three-fold increased risk for severe disease. Here, there was evidence that serum IL-17A protein is negatively correlated with the fraction of blood neutrophils, as well as with airflow in the small airways according to spirometry.…”

Section: Systemic Involvementmentioning

confidence: 99%

“…Interestingly, AGACHE et al [44] recently forwarded evidence for high IL-17A protein in serum constituting an independent risk factor for severe asthma. These investigators found that patients with severe asthma, some treated with a high dose of an inhaled glucocorticoid, have substantially more IL-17A protein in serum compared with patients with mild-to-moderate asthma.…”

Section: Systemic Involvementmentioning

confidence: 99%

“…It remains to be evaluated whether Th17 or Tc17 cells in the airways of patients with asthma share characteristics with the corresponding blood cells [12,13,48,[51][52][53][54][55][56][57]. Moreover, the documentation of expression for IL-17A in invariant natural killer T-cells and in mucosal-associated invariant T-cells from human subjects is intriguing but further study is needed given that there are no published studies addressing these cell types in the airways of patients with asthma [11,13,42,44,48,[50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66].…”

Section: Multiple Cellular Sourcesmentioning

confidence: 99%

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Interleukin-17 cytokine signalling in patients with asthma

Lindén

Dahlén

2014

Eur Respir J

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Asthma remains a global health problem and, therefore, more effective pharmacotherapy is needed. This is particularly true for chronic and severe asthma. In these clinical phenotypes, chronic inflammation involving neutrophils is likely to play a pathogenic role, making it interesting to target cytokine signalling involved in the accumulation of neutrophils. Therefore, it is of interest that the archetype T-helper 17 cell cytokine interleukin (IL)-17A, perhaps also IL-17F, controls neutrophil accumulation, mucus secretion, macrophage mobilisation and smooth muscle reactivity in various experimental airway models. However, much less is known about the involvement of signalling via IL-17 cytokines in humans with asthma. Existing evidence suggests that these cytokines are released from several types of immune cells in asthma and, for IL-17A, there is a local increase associated with disease severity, with the mobilisation of neutrophils and smooth muscle cells locally in the airways. Even though the causative role of IL-17 cytokines remains unclear, there is potential for clinical utility in targeting IL-17A specifically in patients with moderate-to-severe asthma and high reversibility. There is a need for new and well-powered clinical investigations of signalling via IL-17 cytokines in this clinical phenotype. @ERSpublications There is potential utility for drugs targeting IL-17 cytokine signalling in a sub-group of patients with asthma

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“…might be involved in mediating granulocytic influx in the absence of B lymphocytes. IL-6 and IL-17A have been associated with granulocyte recruitment in other allergy models, [37][38][39][40][41] so we assessed the levels of these cytokines in the fungal model to determine whether they could be responsible for the increased granulocytic inflammation seen in the absence of B cells. After the third conidia challenge, the levels of IL-6 ( Figure 9a) and IL-17A ( Figure 9b) were significantly higher in the BAL fluid of J H 2/2 mice than in the BAL fluid of BALB/c mice, consistent with increased numbers of neutrophils and eosinophils in the BAL compartment of the J H 2/2 mice at D3 (IH3).…”

Section: Fungal Conidia Inhalation Significantly Increases Collagen Dmentioning

confidence: 99%

B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma

et al. 2014

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Sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. Although B lymphocytes might exacerbate asthma symptoms through the production of IgE, these cells might also be important in the protective response against inhaled fungi. Through cytokine release and T-cell interactions, these lymphocytes might also influence the development and maintenance of airway wall fibrosis. J H 2/2 mice lack the JH gene for the heavy chain component of antibodies, which is critical for B-cell function and survival. These animals have facilitated the elucidation of the role of B lymphocytes in a number of immune responses; however, J H 2/2 mice have not been used to study fungal allergy. In this study, we examined the role of B lymphocytes using an Aspergillus fumigatus murine fungal aeroallergen model that mimics human airway disease that is triggered by environmental fungal exposure. We compared disease progression in sensitized wild-type BALB/c and J H 2/2 mice that were exposed to repeated fungal exposure and found no differences in airway hyperresponsiveness, overall pulmonary inflammation or collagen deposition around the large airways. However, the levels of the Th2-type cytokines IL-4 and IL-13 were significantly attenuated in the airways of J H 2/2 mice relative to the BALB/c controls. By contrast, levels of the inflammatory cytokines IL-17A and IL-6 were significantly elevated in the J H 2/2 animals, and there was significantly more robust airway eosinophilia and neutrophilia than in control animals. Taken together, these findings demonstrate that B lymphocytes help to regulate granulocytic responses to fungal exposure in the pulmonary compartment.

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Increased serum IL-17 is an independent risk factor for severe asthma

Abstract: IL-17 is increased in severe asthma compared to mild/moderate forms of the disease and values above 20 pg/ml are an independent risk factor for severe asthma.

Cited by 223 publications

References 15 publications

Role of dendritic cells: a step forward for the hygiene hypothesis

Role of dendritic cells: a step forward for the hygiene hypothesis

Interleukin-17 cytokine signalling in patients with asthma

B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma

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