Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism

Cates, Elizabeth C.; Fattouh, Ramzi; Jordana, Manel

doi:10.1016/s0091-6749(03)80205-1

Cited by 70 publications

(102 citation statements)

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“…In models of allergic diseases, Ab neutralization of GM-CSF attenuated eosinophil inflammation and AHR (9,11). The phenotype in GM-CSF Ϫ/Ϫ mice in the present study is similar, but not identical, to these reports.…”

Section: Discussionsupporting

confidence: 83%

“…In a study on inhalation of diesel exhaust particles in mice, AHR and Clara cell hyperplasia were attenuated by anti-GM-CSF Ab (10). In a report on intranasal exposure to house dust mite, administration of a GM-CSF-neutralizing mAb markedly reduced inflammatory responses in the lung and spleen and resulted in reduced Th2 effector cells and airway eosinophilia (11).…”

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confidence: 99%

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Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation

Rolph

Hansbro

et al. 2008

The Journal of Immunology

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GM-CSF plays an important role in inflammation by promoting the production, activation, and survival of granulocytes and macrophages. In this study, GM-CSF knockout (GM-CSF−/−) mice were used to investigate the role of GM-CSF in a model of allergic airway inflammation. In allergic GM-CSF−/− mice, eosinophil recruitment to the airways showed a striking pattern, with eosinophils present in perivascular areas, but almost completely absent in peribronchial areas, whereas in wild-type mice, eosinophil infiltration appeared in both areas. In the GM-CSF−/− mice, mucus production in the airways was also reduced, and eosinophil numbers were markedly reduced in the bronchoalveolar lavage (BAL)3 fluid. IL-5 production was reduced in the lung tissue and BAL fluid of GM-CSF−/− mice, but IL-4 and IL-13 production, airway hyperresponsiveness, and serum IgE levels were not affected. The presence of eosinophils in perivascular but not peribronchial regions was suggestive of a cell migration defect in the airways of GM-CSF−/− mice. The CCR3 agonists CCL5 (RANTES) and CCL11 (eotaxin-1) were expressed at similar levels in GM-CSF−/− and wild-type mice. However, IFN-γ mRNA and protein were increased in the lung tissue and BAL fluid in GM-CSF−/− mice, as were mRNA levels of the IFN-γ-inducible chemokines CXCL9 (Mig), CXCL10 (IP-10), and CXCL11 (I-Tac). Interestingly, these IFN-γ-inducible chemokines are natural antagonists of CCR3, suggesting that their overproduction in GM-CSF−/− mice contributes to the lack of airway eosinophils. These findings demonstrate distinctive abnormalities to a model of allergic asthma in the absence of GM-CSF.

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Section: Discussionsupporting

confidence: 83%

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confidence: 99%

Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation

Rolph

Hansbro

et al. 2008

The Journal of Immunology

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“…Initially we determined if miRNAs were expressed in the airways in response to allergen exposure by employing a well characterized and clinically relevant BALB/c mouse model of HDM-induced allergic asthma (24). In this model, allergen exposure within the airways results in direct sensitization and the Author contributions: J.M., A.C., S.P., and P.S.F.…”

Section: Exposure Of the Airways To House Dust Mite Increases The Expmentioning

confidence: 99%

Antagonism of microRNA-126 suppresses the effector function of T _H 2 cells and the development of allergic airways disease

Mattes

Collison²,

Plank³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

399

370

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Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T H2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of TH2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in sensing molecular patterns and in programming adaptive T cell responses. Here we show that in vivo activation of TLR4 by house dust mite antigens leads to the induction of allergic disease, a process that is associated with expression of a unique subset of small, noncoding microRNAs. Selective blockade of microRNA (miR)-126 suppressed the asthmatic phenotype, resulting in diminished T H2 responses, inflammation, airways hyperresponsiveness, eosinophil recruitment, and mucus hypersecretion. miR-126 blockade resulted in augmented expression of POU domain class 2 associating factor 1, which activates the transcription factor PU.1 that alters T H2 cell function via negative regulation of GATA3 expression. In summary, this study presents a functional connection between miRNA expression and asthma pathogenesis, and our data suggest that targeting miRNA in the airways may lead to anti-inflammatory treatments for allergic asthma.animal model ͉ asthma ͉ inflammation ͉ microRNA ͉ TH2 cytokines

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“…Lung epithelium-derived GM-CSF is a critical regulator of CD11b + DC-mediated Th2 cell priming GM-CSF is a critical cytokine for the development of allergic asthma as its blockade with neutralizing Abs abrogates the development of Th2 responses (41,42). However, little is known about how GM-CSF potentiates Th2 priming.…”

Section: Cd11bmentioning

confidence: 99%

GM-CSF–Licensed CD11b+ Lung Dendritic Cells Orchestrate Th2 Immunity to Blomia tropicalis

Zhou

Schlitzer

et al. 2014

The Journal of Immunology

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The Blomia tropicalis dust mite is prevalent in tropical and subtropical regions of the world. Although it is a leading cause of asthma, little is known how it induces allergy. Using a novel murine asthma model induced by intranasal exposure to B. tropicalis, we observed that a single intranasal sensitization to B. tropicalis extract induces strong Th2 priming in the lung draining lymph node. Resident CD11b+ dendritic cells (DCs) preferentially transport Ag from the lung to the draining lymph node and are crucial for the initiation of Th2 CD4+ T cell responses. As a consequence, mice selectively deficient in CD11b+ DCs exhibited attenuated Th2 responses and more importantly did not develop any allergic inflammation. Conversely, mice deficient in CD103+ DCs and CCR2-dependent monocyte-derived DCs exhibited similar allergic inflammation compared with their wild-type counterparts. We also show that CD11b+ DCs constitutively express higher levels of GM-CSF receptor compared with CD103+ DCs and are thus selectively licensed by lung epithelial-derived GM-CSF to induce Th2 immunity. Taken together, our study identifies GM-CSF–licensed CD11b+ lung DCs as a key component for induction of Th2 responses and represents a potential target for therapeutic intervention in allergy.

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Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism

Cited by 70 publications

References 0 publications

Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation

Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation

Antagonism of microRNA-126 suppresses the effector function of T _H 2 cells and the development of allergic airways disease

GM-CSF–Licensed CD11b+ Lung Dendritic Cells Orchestrate Th2 Immunity to Blomia tropicalis

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Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism

Cited by 70 publications

References 0 publications

Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation

Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation

Antagonism of microRNA-126 suppresses the effector function of T H 2 cells and the development of allergic airways disease

GM-CSF–Licensed CD11b+ Lung Dendritic Cells Orchestrate Th2 Immunity to Blomia tropicalis

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About

Antagonism of microRNA-126 suppresses the effector function of T _H 2 cells and the development of allergic airways disease