Abstract
Celiac disease represents a complex autoimmune disorder triggered by gluten exposure in genetically susceptible individuals. Despite extensive research into celiac disease pathogenesis, the interplay between genetic susceptibility, epithelial barrier dysfunction, and immune activation remains incompletely understood. This study uses a Boolean network model of Celiac disease that integrates epithelial cell dynamics, immune signaling pathways, and environmental triggers to provide a deeper understanding of the mechanism of the disease. By using an existing epithelial cell Boolean framework with celiac-specific molecular pathways, we created a computational model comprising of 191 nodes and 701 edges representing key signaling components. We incorporated specific pathways crucial to celiac pathogenesis, including HLA-DQ2 signaling, CXCR3-mediated inflammation, IL-15 cytotoxicity, and zonulin-regulated barrier function. We ran simulations under various conditions revealing that barrier integrity serves as a critical piece for disease activation. Our model successfully reproduced several key features of celiac disease, including the persistence of inflammation after gluten withdrawal through self-sustaining autocrine loops, via the CXCR3 signaling pathway. This computational approach provides new insights into celiac disease pathogenesis by identifying epithelial barrier function as a critical disease determinant, characterizing self-sustaining inflammatory circuits, and demonstrating how IL-15 disrupts tight junction integrity through effects on zonulin and ZO-1. The model offers future insight for in silico testing of therapeutic strategies targeting these pathways and advances our understanding of the complex network dynamics underlying autoimmune disorders. The next steps could include implementing a multiscale tissue model of the gut to simulate tissue remodeling and immune cell interactions. Another piece of future work of this project could include integrating patient-specific modeling.
Advisor
Erśebet, Regan
Second Advisor
Brandley, Nicholas
Department
Biology
Recommended Citation
Beazley, Andrew, "Boolean Modeling of Epithelial Cell Responses in Celiac Disease Pathogenesis" (2025). Senior Independent Study Theses. Paper 11583.
https://openworks.wooster.edu/independentstudy/11583
Disciplines
Digestive System Diseases | Disease Modeling | Immune System Diseases | Medical Education
Keywords
Celiac disease, CXCR3, IL-15, Zo-1, Zonulin, Gluten, Epithelial barrier dysfunction, Autocrine loop
Publication Date
2025
Degree Granted
Bachelor of Arts
Document Type
Senior Independent Study Thesis
© Copyright 2025 Andrew Beazley