Mathematical modelling of immune-mediated villi damage in celiac disease: Th1/Th2 dynamics under gluten exposure and withdrawal

This study presents a novel mathematical model to investigate the immune-mediated dynamics of intestinal villi in celiac disease under varying levels of gluten exposure. The model captures the nonlinear interactions between pro-inflammatory (Th1) and regulatory (Th2) T-helper cells and their influence on villous regeneration and destruction. Three gluten scenarios are explored: gluten-free, partial-gluten and gluten-present conditions. Simulations reveal distinct immune outcomes, including full villous recovery in the absence of gluten, progressive atrophy under intermediate exposure and near-complete destruction with sustained gluten intake. Sensitivity analyses across multiple time points identify key regulatory and inflammatory parameters that govern villous behavior. The findings demonstrate how immune polarization — shaped by gluten exposure — drives mucosal outcomes and highlight critical thresholds beyond which immune regulation fails. This framework provides mechanistic insight and a quantitative basis for guiding future therapeutic strategies aimed at restoring immune balance in gluten-related intestinal disorders.