IL-4 receptor alpha blockade dampens allergic inflammation and upregulates IL-17A expression to promote S aureus clearance in antigen sensitized mouse skin

McGurk, Alex; Strakosha, Maria; Vega-Mendoza, Daniela; Smith, Sharon H.; Stafstrom, Kelsey; Elkins, Megan; Chou, Janet; Wang, Yui‐Hsi

doi:10.1016/j.jaci.2023.05.025

Cited by 6 publications

(1 citation statement)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several other molecules are shown to be induced by VIP in allergic and autoimmune diseases, including TSLP, TGF-β, and VCAM-1, all of which are implicated in the pathogenesis of EoE [80][81][82]. Several studies have shown that targeting eosinophil mast cell receptors or VIP receptors improves the pathogenesis of allergic diseases [32,[83][84][85][86][87][88].…”

Section: Discussionmentioning

confidence: 99%

Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis

Yadavalli,

Upparahalli Venkateshaiah,

Verma

et al. 2024

Cells

View full text Add to dashboard Cite

Background and Aims: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. Methods: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. Results: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. Conclusions: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

show abstract