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  Protease allergens as initiators–regulators of allergic inflammation

Soh, W. T., Zhang, J., Hollenberg, M. D., Vliagoftis, H., Rothenberg, M. E., Sokol, C. L., et al. (2023). Protease allergens as initiators–regulators of allergic inflammation. Allergy: European Journal of Allergy and Clinical Immunology, 78(5), 1148-1168. doi:10.1111/all.15678.

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Allergy - 2023 - Soh.pdf (Publisher version), 15MB
 
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Soh, Wai Tuck1, Author           
Zhang, Jihui, Author
Hollenberg, Morley D., Author
Vliagoftis, Harissios, Author
Rothenberg, Marc E., Author
Sokol, Caroline L., Author
Robinson, Clive, Author
Jacquet, Alain, Author
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1Research Group of Quantitative and Computational Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350226              

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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.

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Language(s): eng - English
 Dates: 2023-02-162023-05
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1111/all.15678
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Title: Allergy: European Journal of Allergy and Clinical Immunology
Source Genre: Journal
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Publ. Info: Hoboken, USA : Wiley
Pages: - Volume / Issue: 78 (5) Sequence Number: - Start / End Page: 1148 - 1168 Identifier: ISSN: 0105-4538
CoNE: https://pure.mpg.de/cone/journals/resource/110976549881407