House Dust Mite Interactions with Airway Epithelium: Role in Allergic Airway Inflammation

Gandhi, Vivek; Davidson, Courtney; Asaduzzaman, Muhammad; Nahirney, Drew; Vliagoftis, Harissios

doi:10.1007/s11882-013-0349-9

Cited by 61 publications

(57 citation statements)

References 98 publications

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“…LPS is part of the outer membrane of Gram-negative bacteria and induces airway inflammation and hyperresponsiveness . HDM allergen is a well-studied inducer of allergic airway inflammation (Gandhi et al, 2013). In addition, both acute and chronic corn pollen exposure induces allergic airway inflammation (Card, J.W., et al, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Polymerase Chain Reaction Analysis of the MouseCyp2jSubfamily: Tissue Distribution and Regulation

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Quantitative Polymerase Chain Reaction Analysis of the MouseCyp2jSubfamily: Tissue Distribution and Regulation

et al. 2015

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“…The house dust mite (HDM) is a major source of indoor allergens and represents a significant factor in the development of respiratory allergic disease [1]. Clinical manifestations of HDM respiratory allergic disease include allergic rhinitis and allergic asthma, and the frequent comorbidity of the two underlines the continuity of the airways [2,3].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of SQ house dust mite (HDM) SLIT-tablet treatment of HDM allergic asthma

Canonica

Virchow

Zieglmayer

et al. 2016

Expert Review of Clinical Immunology

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Introduction: In the treatment of house dust mite (HDM) respiratory allergic disease, allergy immunotherapy constitutes an add-on treatment option targeting the underlying immunological mechanisms of allergic disease. However, for the treatment of HDM allergic asthma, the use of subcutaneous allergy immunotherapy (SCIT) has been limited by the risk of systemic adverse events. Thus, sublingually administered allergy immunotherapy (SLIT) has been investigated as a treatment option with an improved tolerability profile that allows for safer treatment of patients with HDM allergic asthma. Areas covered: In this Drug Profile, we provide a review of the clinical data behind the SQ HDM SLITtablet, which was recently approved for the treatment of HDM allergic asthma and allergic rhinitis by regulatory authorities in several European countries. Expert commentary: The SQ HDM SLIT-tablet is the first allergy immunotherapy to be tested prospectively in patients with asthma, and to favorably modify patient relevant end points such as requirement for inhaled corticosteroid (ICS) or the time to first asthma exacerbation upon ICS reduction, suggesting that SQ HDM SLIT-tablet treatment may contribute to improving overall asthma control.

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“…In patients, an increase in the number of OX40-and OX40L-positive cells in mild asthmatic patients has been shown to correlate with the number of eosinophils and IL-4 + cells in the bronchial submucosa [20] and serum. Similarly, OX40L has been noted to be increased in asthmatic children and adults and was associated with increased severity and persistence of disease [21,22].We have sought to expand the current knowledge surrounding the role of OX40 in allergic lung inflammation by using in vivo and in vitro models driven by house dust mite (HDM) allergen, known to be a common driver of asthmatic disease [23]. Chronic exposure to inhaled allergens induces an inflammatory response in the lung resulting in clinical symptoms of asthma.…”

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OX40 blockade inhibits house dust mite driven allergic lung inflammation in mice and in vitro allergic responses in humans

et al. 2015

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The costimulatory receptor OX40 is expressed on activated T cells and regulates T-cell responses. Here, we show the efficacy and mechanism of action of an OX40 blocking antibody using the chronic house dust mite (HDM) mouse model of lung inflammation and in vitro HDM stimulation of cells from HDM allergic human donors. We have demonstrated that OX40 blockade leads to a reduction in the number of eosinophils and neutrophils in the lavage fluid and lung tissue of HDM sensitized mice. This was accompanied by a decrease in activated and memory CD4 + T cells in the lungs and further analysis revealed that both the Th2 and Th17 populations were inhibited. Improved lung function and decreased HDM-specific antibody responses were also noted. Significantly, efficacy was observed even when anti-OX40 treatment was delayed until after inflammation was established. OX40 blockade also inhibited the release of the Th2 cytokines IL-5 and IL-13 from cells isolated from HDM allergic human donors. Altogether, our data provide evidence of a role of the OX40/OX40L pathway in ongoing allergic lung inflammation and support clinical studies of a blocking OX40 antibody in Th2 high severe asthma patients.Keywords: Allergic asthma r House dust mite r Lung inflammation r Memory T cells r OX40Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction OX40 (also known as CD134, TNFRSF4, ACT35, or TXGP1L) is a membrane-bound receptor belonging to the TNF receptor superfamily, which includes 4-1BB, CD27, CD30, and CD40. This costimulatory receptor is not expressed on resting T cells, but is transiently expressed on activated T cells after ligation of the TCR, with sequential engagement of CD28 and OX40 being required for optimal T-cell proliferation and survival [1]. Ligation of OX40 on activated T cells leads to enhanced cytokine production and proliferation of both CD4 + and CD8 + T cells [2,3] and can contribute to both ongoing Th1 and Th2 responses [4,5]. OX40 costimulationCorrespondence: Diane Marshall e-mail: diane.marshall@ucb.com prolongs T-cell survival beyond the initial effector phase of the immune response and increases the number of memory T cells through inhibition of effector T-cell death. This long-term survival of T cells via OX40 is thought to be a consequence of maintaining high levels of antiapoptotic proteins, such as Bcl-2, 7]. The ligand for OX40, OX40L, is a member of the TNF family and is expressed on activated APC, including B cells, macrophages, Langerhans cells, and dendritic cells (DCs). Other cell types that are reported to express OX40L include mast cells, NK cells, airway smooth muscle cells, endothelial cells, and platelets [8]. * These authors are co-first authors.C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 1116-1128 Immunomodulation 1117Asthma is a chronic inflammatory disease of the airways in which many cells and mediators are involved. It is now clear that asthma is a heterogenic disease a...

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House Dust Mite Interactions with Airway Epithelium: Role in Allergic Airway Inflammation

Cited by 61 publications

References 98 publications

Quantitative Polymerase Chain Reaction Analysis of the MouseCyp2jSubfamily: Tissue Distribution and Regulation

Quantitative Polymerase Chain Reaction Analysis of the MouseCyp2jSubfamily: Tissue Distribution and Regulation

Efficacy and safety of SQ house dust mite (HDM) SLIT-tablet treatment of HDM allergic asthma

OX40 blockade inhibits house dust mite driven allergic lung inflammation in mice and in vitro allergic responses in humans

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