Chronic inflammatory diseases, such as inflammatory bowel disease, psoriatic arthritis, and lupus, impose a significant public health burden. Despite our understanding of type 17 immune responses, the mechanisms by which aberrant type 17 inflammation is triggered and sustained remain unclear. Given the critical role of group 3 innate lymphoid cells (ILC3s) in immune homeostasis, this project aims to define how ILC3s can cause sustained inflammation and identify the molecular pathways governing this dysregulation. The findings will provide fundamental insights into immune regulation, to advance understanding of immune-mediated diseases, and improve therapeutic strategies. Aim 1 will determine the impact of ILC3 abundance on tissue homeostasis and inflammation by investigating how ILC3s influence T cell numbers, function, and inflammatory programs, contributing to tissue homeostasis. Aim 2 will define the role of ZBTB transcription factors in ILC3 maintenance and type 17 inflammation by examining how they regulate ILC3 populations, modulating immune responses from a homeostatic type 17 program to a pathogenic inflammatory state. To achieve these aims, the project will leverage a physiologically relevant A20 knock-in mouse model, which develops spontaneous mucosal inflammation mimicking human disease. The study will integrate in vivo immune profiling, transcriptomic analysis, and chromatin mapping to uncover how ILC3s contribute to type 17 dysregulation. By elucidating how ILC3s and transcription factors drive inflammation, this project will uncover key epigenetic and immune regulatory mechanisms. Furthermore, these studies open up potentially new therapeutic targets for chronic inflammatory diseases. These findings will provide a foundation for developing novel interventions that restore immune balance/homeostasis and prevent pathogenic inflammation. Dr. Bowman is a clinical research fellow at the University of California, San Francisco. Prior research training has g