Poster #016
Using iPSCs to Study Paneth Cell Function in Crohn’s Disease
Mentor: Monica Wagner, PhD
Paneth cells (PCs) secrete antimicrobial peptides such as lysozyme to protect against pathogenic bacteria. In individuals with Crohn’s Disease (a variant of Inflammatory Bowel Disease) carrying a single nucleotide polymorphism (SNP) in gene ATG16L1, PCs often display abnormal morphology/function. To study how this SNP affects PC activity, we compared lysozyme activity between human intestinal organoids (HIOs) derived from induced pluripotent stem cells carrying the SNP and genetically corrected HIOs. To mimic bacterial exposure and stimulate lysozyme secretion, PCs were treated with MDP (muramyl dipeptide). Lysozyme expression was assessed using quantitative PCR and activity tested using EnzChek® Lysozyme Activity Assay (measures lysozyme activity in degrading bacteria cell wall components). Risk variant organoids showed reduced lysozyme activity upon MDP addition. However, corrected organoids displayed a fourfold increase. These results suggest that the ATG16L1 risk variant lowers PCs’ immune function, while correcting the mutation improves lysozyme activity in PCs, restoring the pathogenic response.