# Investigating the consequences of tape-stripping in ovalbumin-induced allergic mouse model: From physiology to gene regulation

## TL;DR

This study shows that damaging the skin barrier worsens food allergies in mice by disrupting gut health and immune balance.

## Contribution

The study identifies key genes and pathways linking skin barrier disruption to food allergy exacerbation via the skin-gut axis.

## Key findings

- Tape-stripping worsens allergic symptoms and intestinal inflammation in mice.
- Skin barrier damage elevates IgE, mast cells, and Tregs while reducing gut tight junction proteins.
- Acta2, Kdr, and Cxcr4 are key genes linking barrier dysfunction to allergic inflammation.

## Abstract

Food allergy is a growing global health concern, with increasing prevalence and significant impacts on patients quality of life. Epithelial barrier dysfunction, particularly through the skin-gut axis, has emerged as a critical factor in food allergy pathogenesis. However, the precise mechanisms linking epithelial barrier disruption to immune dysregulation remain poorly understood. This study investigates the effects of tape-stripping-induced epithelial barrier damage on the exacerbation of ovalbumin (OVA)-induced food allergy in a murine model, with a focus on histopathological, immunological, and transcriptomic changes.

Female BALB/c mice were randomly assigned to three experimental groups for comparison: Control, OVA (OVA-sensitized/challenged), and OVA + T (OVA-sensitized/challenged with additional tape-stripping). Mice in the OVA group were sensitized and challenged with ovalbumin, while the OVA + T group underwent the same OVA protocol plus repeated tape-stripping to simulate epithelial barrier disruption. Allergic responses were evaluated using a comprehensive approach, including histopathological analysis, quantification of serum biomarkers (IgE, histamine, IL-6, IgG1), immune cell profiling via flow cytometry, and Western blot analysis of tight junction proteins such as occludin, Zonula Occludens (ZO)-1, and claudin. RNA sequencing-based transcriptomic analysis of jejunum tissues identified dysregulated pathways through integrated bioinformatics analyses (differential expression, pathway enrichment, and PPI network), with subsequent qRT-PCR validation pinpointing key target genes.

Tape-stripping exacerbated allergic symptoms, including diarrhea and elevated rectal temperature, and induced significant histopathological changes in both skin and intestinal tissues, characterized by increased inflammatory cell infiltration and mast cell accumulation. Serum analysis revealed elevated levels of IgE, histamine, IL-6, and IgG1, indicating a heightened allergic state. Flow cytometry demonstrated an increase in CD4+ Foxp3+ regulatory T cells (Tregs) and IgE + cells in the spleen, suggesting systemic immune dysregulation. Western blot analysis confirmed the downregulation of tight junction proteins, indicating compromised intestinal barrier integrity. Transcriptomic analysis identified 444 differentially expressed genes (DEGs) in the jejunum, with significant enrichment in pathways related to calcium signaling, cytokine-cytokine receptor interactions, PI3K-Akt signaling, and MAPK signaling. PPI network analysis identified Acta2, Kdr, and Cxcr4 as key target genes mediating tape-stripping-induced food allergy exacerbation.

This study demonstrates that tape-stripping exacerbates food allergy by disrupting epithelial barrier integrity, inducing systemic immune dysregulation, and altering gene expression in intestinal tissues. The identification of key molecular pathways and target genes—particularly Acta2, Kdr, and Cxcr4, which are associated with angiogenesis and inflammatory responses—reveals novel mechanistic insights into food allergy exacerbation and proposes actionable therapeutic targets for simultaneous barrier repair and immune modulation. These findings underscore the importance of the skin-gut axis in food allergy pathogenesis and offer a foundation for developing targeted interventions to manage and prevent allergic diseases. Further research is needed to validate these findings and explore therapeutic strategies targeting the identified pathways.

•Tape-stripping-induced skin barrier damage exacerbates allergic symptoms and intestinal inflammation in a murine food allergy model.•Barrier disruption drives systemic immune dysregulation, elevating IgE, mast cells, and splenic Tregs, while reducing intestinal tight junction proteins.•PPI network analysis reveals Acta2, Kdr, and Cxcr4 as hub genes linking barrier dysfunction to allergic inflammation.•Findings underscore the skin-gut axis as a therapeutic target for restoring epithelial integrity and modulating immune response in food allergy.

Tape-stripping-induced skin barrier damage exacerbates allergic symptoms and intestinal inflammation in a murine food allergy model.

Barrier disruption drives systemic immune dysregulation, elevating IgE, mast cells, and splenic Tregs, while reducing intestinal tight junction proteins.

PPI network analysis reveals Acta2, Kdr, and Cxcr4 as hub genes linking barrier dysfunction to allergic inflammation.

Findings underscore the skin-gut axis as a therapeutic target for restoring epithelial integrity and modulating immune response in food allergy.