Soh, WT; Zhang, J; Hollenberg, MD; Vliagoftis, H; Rothenberg, ME; Sokol, CL; Robinson, C; Jacquet, A
(2023)
Protease allergens as initiators-regulators of allergic inflammation.
Allergy, 78 (5).
pp. 1148-1168.
ISSN 1398-9995
https://doi.org/10.1111/all.15678
SGUL Authors: Robinson, Clive
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Abstract
Tremendous progress in the last few years has been made to explain how seemingly harmless environmental proteins from different origins can induce potent Th2-biased inflammatory responses. Convergent findings have shown the key roles of allergens displaying proteolytic activity in the initiation and progression of the allergic response. Through their propensity to activate IgE-independent inflammatory pathways, certain allergenic proteases are now considered as initiators for sensitization to themselves and to non-protease allergens. The protease allergens degrade junctional proteins of keratinocytes or airway epithelium to facilitate allergen delivery across the epithelial barrier and their subsequent uptake by antigen-presenting cells. Epithelial injuries mediated by these proteases together with their sensing by protease-activated receptors (PARs) elicit potent inflammatory responses resulting in the release of pro-Th2 cytokines (IL-6, IL-25, IL-1β, TSLP) and danger-associated molecular patterns (DAMPs; IL-33, ATP, uric acid). Recently, protease allergens were shown to cleave the protease sensor domain of IL-33 to produce a super-active form of the alarmin. At the same time, proteolytic cleavage of fibrinogen can trigger TLR4 signaling, and cleavage of various cell surface receptors further shape the Th2 polarization. Remarkably, the sensing of protease allergens by nociceptive neurons can represent a primary step in the development of the allergic response. The goal of this review is to highlight the multiple innate immune mechanisms triggered by protease allergens that converge to initiate the allergic response.
Item Type: | Article | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Additional Information: | This is the peer reviewed version of the following article: Soh, WT, Zhang, J, Hollenberg, MD, et al. Protease allergens as initiators–regulators of allergic inflammation. Allergy. 2023; 78: 1148- 1168, which has been published in final form at https://doi.org/10.1111/all.15678. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Keywords: | IL-33, protease allergen; epithelial cell, protease-activated receptor, sensory neuron, IL-33, protease allergen, epithelial cell, protease-activated receptor, sensory neuron, IL-33, protease allergen; epithelial cell, protease-activated receptor, sensory neuron, 1107 Immunology, Allergy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Infection and Immunity Research Institute (INII) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Allergy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 1398-9995 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Language: | eng | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Publisher License: | Publisher's own licence | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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PubMed ID: | 36794967 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Web of Science ID: | WOS:000939693400001 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/115396 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Publisher's version: | https://doi.org/10.1111/all.15678 |
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