Dataset Information

A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure.

ABSTRACT: Allergic asthma is a chronic immune-inflammatory disease of the airways. Despite aeroallergen exposure being universal, allergic asthma affects only a fraction of individuals. This is likely related, at least in part, to the extent of allergen exposure. Regarding house dust mite (HDM), we previously identified the threshold required to elicit allergic responses in BALB/c mice. Here, we investigated the impact of an initial immune perturbation on the response to sub-threshold HDM exposure. We show that transient GM-CSF expression in the lung facilitated robust eosinophilic inflammation, long-lasting antigen-specific Th2 responses, mucus production and airway hyperresponsiveness. This was associated with increased IL-33 levels and activated CD11b(+) DCs expressing OX40L. GM-CSF-driven allergic responses were significantly blunted in IL-33-deficient mice. IL-33 was localized on alveolar type II cells and in vitro stimulation of human epithelial cells with GM-CSF enhanced intracellular IL-33 independently of IL-1?. Likewise, GM-CSF administration in vivo resulted in increased levels of IL-33 but not IL-1?. These findings suggest that exposures to environmental agents associated with GM-CSF production, including airway infections and pollutants, may decrease the threshold of allergen responsiveness and, hence, increase the susceptibility to develop allergic asthma through a GM-CSF/IL-33/OX40L pathway.

SUBMITTER: Llop-Guevara A

PROVIDER: S-EPMC3925157 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure.

Llop-Guevara Alba A Chu Derek K DK Walker Tina D TD Goncharova Susanna S Fattouh Ramzi R Silver Jonathan S JS Moore Cheryl Lynn CL Xie Juliana L JL O'Byrne Paul M PM Coyle Anthony J AJ Kolbeck Roland R Humbles Alison A AA Stämpfli Martin R MR Jordana Manel M

PloS one 20140214 2

Allergic asthma is a chronic immune-inflammatory disease of the airways. Despite aeroallergen exposure being universal, allergic asthma affects only a fraction of individuals. This is likely related, at least in part, to the extent of allergen exposure. Regarding house dust mite (HDM), we previously identified the threshold required to elicit allergic responses in BALB/c mice. Here, we investigated the impact of an initial immune perturbation on the response to sub-threshold HDM exposure. We sho ...[more]

PMID: 24551140

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Project description:BackgroundOne of the important pathogeneses of eustachian tube dysfunction (ETD) is nasal inflammatory disease. The prevalence of allergic rhinitis (AR) in adults ranges from 10 to 30% worldwide. However, research on the status of eustachian tubes in AR patients is still very limited.MethodsThis prospective controlled cross-sectional study recruited 59 volunteers and 59 patients with AR from Sun Yat-sen Memorial Hospital. Visual analogue scale (VAS) scores for AR symptoms and seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) scores were collected for both groups. Nasal endoscopy, tympanography and eustachian tube pressure measurement (tubomanometry, TMM) were used for objective assessment. All AR patients underwent 1 month of treatment with mometasone furoate nasal spray and oral loratadine. Then, the nasal condition and eustachian tube status were again evaluated.ResultsTMM examination revealed that 22 patients (39 ears, 33.1%) among the AR patients and 5 healthy controls (7 ears, 5.9%) had abnormal eustachian pressure. Twenty-two AR patients (37.3%) and 9 healthy controls had an ETDQ-7 score ≥ 15. With regard to nasal symptoms of AR, the VAS scores of nasal obstruction were correlated with the ETDQ-7 scores, and the correlation coefficient was r = 0.5124 (p < 0.0001). Nasal endoscopic scores were also positively correlated with ETDQ-7 scores, with a correlation coefficient of 0.7328 (p < 0.0001). After 1 month of treatment, VAS scores of nasal symptoms, endoscopic scores and ETDQ-7 scores were significantly decreased in AR patients (p < 0.0001), and TMM examination also suggested that eustachian tube function was significantly improved after treatment (p < 0.0001).ConclusionsAR patients, especially those with severe nasal obstruction, could have ETD. The local conditions of the pharyngeal orifices of the eustachian tubes are closely related to the symptoms of ETD. After treatment with nasal glucocorticoids and oral antihistamines, eustachian tube function can significantly improve as nasal symptoms subside.Trial registration Chinese Clinical Trial Registery (ChiCTR2000029071) Registered 12 January 2020-Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=48328&htm=4.

Dataset Information

A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure.

Publications

A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure.

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