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- W4313356108 abstract "Abstract Allergic diseases, which have escalated in prevalence in recent years, arise as a result of maladaptive immune responses to ubiquitous environmental proteins. Arthropods, such as mites, cockroaches, and crustaceans, are a major source of allergens, yet the majority of us live with or consume these invertebrates with no ill effects. Recent discoveries have raised the possibility that altered innate immune recognition of allergens, through pattern recognition receptors (PRR), may underlie disease susceptibility. Here, we identify the PRR, dectin-1 (CLEC7A), as a key receptor in mediating protection against dust mite-driven type 2 immune responses through the inhibition of epithelial cell IL-33 production, and the downstream recruitment of IL-13-producing innate lymphoid 2 cells (ILC2). Surprisingly, we observed that this effect was not mediated by the prototypical dectin-1 ligand, β-glucan, within allergen extracts. We discovered a novel protein ligand conserved across the arthropod phyla, sensing of which confers protection against aberrant type 2 responses that drive respiratory allergy and food anaphylaxis in mice. While this homeostatic pathway is functional in respiratory epithelial cells from healthy humans, dectin-1 is repressed in asthmatics and patients with chronic-rhinosinusitis. Importantly, we report a novel SNP in CLEC7A in the SAGE and GALAII GWAS studies, associated with lung function. Collectively, our findings reveal a previously unrecognized negative regulatory pathway in which ligation of dectin-1 results in reduction of type 2 immune responses, while disruption of this critical regulatory circuit is associated with susceptibility to a spectrum of allergic disorders." @default.
- W4313356108 created "2023-01-06" @default.
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- W4313356108 date "2017-05-01" @default.
- W4313356108 modified "2023-09-27" @default.
- W4313356108 title "Suppression of type-2 mediated allergic diseases by dectin-1" @default.
- W4313356108 doi "https://doi.org/10.4049/jimmunol.198.supp.194.1" @default.
- W4313356108 hasPublicationYear "2017" @default.
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