Project Grant R01DK141146

This Project Grant award of $1,328,326.00 from the National Institute of Diabetes and Digestive and Kidney Diseases (CFDA 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research) supports research on the regulation of CD39 expression in gamma delta intraepithelial lymphocytes (gd IELs) and its impact on immunometabolism and function. The research aims to elucidate the mechanisms by which CD39 expression is regulated in gd IELs, understand the coupling between CD39 and gd IEL bioenergetic capacity, and investigate the relationship between antibiotic treatment and gd IEL functionality in pouchitis. The award will fund a combination of ex vivo IEL culture, IEL/enteroid co-culture, single cell metabolomics assays, and mouse model studies to dissect the molecular mechanisms involved in the upregulation of CD39 and immunometabolism in response to the microbiota. The findings are expected to further the understanding of cellular and molecular mechanisms that amplify gd IEL regulatory function to maintain mucosal homeostasis, with the ultimate goal of preventing disease relapse in inflammatory bowel disease patients.