Year: 2025
Type: article
Abstract: Description Dysregulated type 2 immune responses mediate airway allergic diseases such as asthma and chronic rhinosinusitis. We previously showed that epithelial dectin-1 interaction with invertebrate tropomyosin, a ubiquitous component of house dust mite (HDM), protects against aberrant type 2 responses by inhibiting interleukin-33 (IL-33)-mediated recruitment of innate lymphoid type 2 cells (ILC2s). In susceptible individuals, this protective mechanism is impaired, resulting in elevated IL-33 production. Using a murine model of airway allergy, we found dectin-1 represses the induction of a distinct HDM-elicited epithelial cell population that co-express IL-33 and HIF-1a. Notably, HIF-1a is exclusively expressed by IL-33hi epithelial cells. It is known that allergen-induced IL-33 release from airway epithelium is due to elevation in oxidative stress, a known driver of HIF-1a activation. We found that HDM increases oxidative stress in the epithelium. Overexpressing dectin-1 in human bronchial epithelial cells blocks this by elevating glutathione (GSH) levels, a vital cellular antioxidant. Thus, dectin-1 signaling inhibits HDM-induced cellular oxidative stress. Accordingly, epithelial dectin-1 signaling represses HIF1A mRNA and prevents HIF-1a activity, as measured by assessing hypoxia-response element (HRE) activity. Therefore, we propose that epithelial dectin-1 signaling inhibits the release of IL-33 by suppressing oxidative stress and subsequent HIF-1a activation. Funding Sources Supported by NIHR01AI127644. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)
Source: The Journal of Immunology
Institution: Johns Hopkins University
Language: English
Topic: IL-33, ST2, and ILC Pathways
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416449004
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