J Immunol. 2025 Aug 24:vkaf207. doi: 10.1093/jimmun/vkaf207. Online ahead of print.
ABSTRACT
Allergic rhinitis (AR) is a respiratory airway disorder characterized by inflammation and barrier dysfunction. The transcription factor specificity protein 1 (SP1), a member of the Sp/Krüppel-like factor family, is known to be associated with inflammation. This study aimed to explore the impacts of SP1 on AR. An AR murine model was developed through multiple intranasal challenges with ovalbumin (OVA). Human nasal epithelial cells (HNEpCs) were cultured at the air-liquid interface (ALI) and treated with IL-13 to create a cell model with barrier damage. Bioinformation samples revealed that SP1 expression was upregulated in nasal epithelial cells of people with AR. High Sp1 expression was observed in AR mice nasal mucosa. Silencing Sp1 reduced nasal rubbing, sneezing, serum levels of IgE, histamine, and nasal swelling in AR mice. Additionally, Sp1 silencing inhibited goblet cell proliferation, eosinophilic infiltration, and levels of IL-4 and IL-13. Sp1 knockdown reversed the elevated fluorescein isothiocyanate-dextran 4 kDa permeability, nasal epithelial cell shedding, and decreased expression of E-cadherin and Claudin-1. In vitro, knocking down SP1 led to an increase in transepithelial electrical resistance and levels of E-cadherin and Claudin-1. Mechanistically, SP1 upregulated forkhead box C1 (FOXC1) expression through transcriptional activity, and FOXC1 overexpression reversed the protective effects of SP1 silencing on epithelial barrier damage. Overall, our findings suggest that SP1 aggravates AR, potentially through the transcriptional activation of SP1 to FOXC1.
PMID:40849888 | DOI:10.1093/jimmun/vkaf207