Single-Cell Mapping of the Gut Epithelium Reveals Paneth Cell Dysfunction and Lysozyme Deficiency in Peanut Allergy
Year: 2026
Type: article
Abstract: BACKGROUND & AIMS: A growing body of evidence links intestinal epithelial cell barrier dysfunction to the development of food allergies. We previously showed that the peanut allergy-susceptible CC027 mouse has increased intestinal permeability. To understand the heterogeneity of the intestinal barrier in peanut allergy susceptibility, we used single-cell RNA sequencing to generate a high-resolution single-cell atlas of the small intestinal epithelium in the naïve CC027 mouse. This can be used to inform patient findings and provide a resource for understanding how epithelial cells contribute to peanut allergy pathogenesis. METHODS: We generated a high-resolution single-cell atlas of the intestinal epithelium of allergy-susceptible, naïve CC027 mice and allergy-prone but orally resistant, naïve C3H/HeJ mice. Histology studies in gastrointestinal tissues from mice and human patients with or without peanut allergy corroborated our findings. RESULTS: Naïve CC027 mice exhibited a reduced proportion of interferon-responsive absorptive enterocytes compared with naïve C3H/HeJ mice, reduced numbers of enteroendocrine cells, and increased numbers of goblet and tuft cells. We found a complete absence of the Paneth cell antimicrobial peptide lysozyme 1 transcript and enrichment of mitochondrial stress pathways in peanut unexposed CC027 mice. Paneth cells from CC027 mice exhibited signs of cell stress by electron microscopy. In patients with peanut allergy, small intestinal biopsies demonstrated decreased Paneth cell-specific lysozyme 1 protein expression. CONCLUSIONS: We establish a single-cell atlas of the intestinal epithelium in a translationally relevant peanut allergy-susceptible mouse model and show a link between intestinal permeability, epithelial-derived interferon responses, and Paneth cell dysfunction in maintaining immune tolerance to dietary antigens.
Authors: Katelyn M. Clough, Ismael Gomez-Martinez, Gabrielle Cannon, Nathan K. VanLandingham, Maria R. Chettoor, Zena Khaled, Sophia Kennedy, Matthew R. Schaner, Benjamin Huan, Gwen W. Lau, Grace Lian, Sophie Silverstein, Caroline Beasley, David S. Weaver, Ariana M. Lacorte, Brady Furey, Sabina A. Mir, Jillann A. Madren, Kristen K. White, Austin J. Hepperla, Terrence S. Furey, Erin C. Steinbach, Shehzad Z. Sheikh
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,430
Funders: Foundation of the American College of Allergy, Asthma & Immunology, North Carolina Biotechnology Center, Leona M. and Harry B. Helmsley Charitable Trust, NIH Office of the Director, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
OpenAlex ID: W7214944752