The aim of this project is to use advanced systems biology methods and large public datasets to investigate the regulation of innate lymphoid cells (ILC3s) in human gut immunity, expanding upon previous research from our group (Mazzurana et al., Cell Res. 2021; Kokkinou et al., Sci. Immunol. 2022). Thus far, this work has succussfully leveraged computational tools and resources provided by SNIC/NAISS to elucidate the molecular mechanisms by which ILC3s regulate immune interactions via TGF-β1 signaling. In this project, computational resources have enabled us to identify and characterize the unique capability of ILC3s to activate latent TGF-β in the small and large intestines under both healthy and inflamed conditions. These findings are featured in a manuscript currently under review, "ILC3s modulate immune-epithelial interactions in the gut via TGF-β1 activation." This project is a crucial resource that supports the Ph.D. thesis work of the main applicant, John Bassett.