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Allergen Delivery Inhibitors: Characterisation of Potent and Selective Inhibitors of Der p 1 and Their Attenuation of Airway Responses to House Dust Mite Allergens
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Int. J. Mol. Sci. 2018, 19(11), 3549; https://doi.org/10.3390/ijms19113549

Cellular and Molecular Events in the Airway Epithelium Defining the Interaction Between House Dust Mite Group 1 Allergens and Innate Defences

1
Institute for Infection & Immunity, St George’s, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom
2
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
*
Author to whom correspondence should be addressed.
Received: 31 August 2018 / Revised: 30 October 2018 / Accepted: 7 November 2018 / Published: 10 November 2018
(This article belongs to the Special Issue Molecular Research on Mucosal Immunity)
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Abstract

Serodominant group 1 allergens of house dust mites (HDMs) are cysteine protease digestive enzymes. By increasing the detection of any allergen by dendritic antigen presenting cells, upregulating inflammatory signalling molecules, and activating cells crucial to the transition from innate to acquired immune responses, the proteolytic activity of these HDM allergens also underlies their behaviour as inhalant allergens. The significance of this property is underlined by the attenuation of allergic responses to HDMs by novel inhibitors in experimental models. The group 1 HDM allergens act as prothrombinases, enabling them to operate the canonical stimulation of protease activated receptors 1 and 4. This leads to the ligation of Toll-like receptor 4, which is an indispensable component in HDM allergy development, and reactive oxidant-regulated gene expression. Intermediate steps involve epidermal growth factor receptor ligation, activation of a disintegrin and metalloproteases, and the opening of pannexons. Elements of this transduction pathway are shared with downstream signalling from biosensors which bind viral RNA, suggesting a mechanistic linkage between allergens and respiratory viruses in disease exacerbations. This review describes recent progress in the characterisation of an arterial route which links innate responses to inhaled allergens to events underpinning the progression of allergy to unrelated allergens. View Full-Text
Keywords: allergen delivery inhibitor; Der p 1; airway epithelium; asthma; TLR4; thrombin; alarmins; ADAM 10; tight junctions allergen delivery inhibitor; Der p 1; airway epithelium; asthma; TLR4; thrombin; alarmins; ADAM 10; tight junctions
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Zhang, J.; Chen, J.; Robinson, C. Cellular and Molecular Events in the Airway Epithelium Defining the Interaction Between House Dust Mite Group 1 Allergens and Innate Defences. Int. J. Mol. Sci. 2018, 19, 3549.

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