Metabolic Intervention of Group 3 Innate Lymphoid Cells (ILC3s) in Intestinal Inflammation.
Group 3 innate lymphoid cells (ILC3s) are the innate counterparts of TH17. As TH17, ILC3s require on the transcription factor RORγt for development and function. Together with TH17, ILC3s contribute to intestinal homeostasis and to defense against pathogenic insults through secretion of IL-22 and IL-17. However, ILC3s and TH17 are differentially regulated: TH17 respond to antigen stimulation, whereas ILC3s respond to soluble factors such as cytokines. Recent studies have shown that cellular metabolism plays a key role in the regulation of immune cells. Proliferation and effector functions of TH17 require a specific mTOR dependent metabolic program that utilizes high rate glycolysis, while mitochondria lipid oxidation and production of reactive oxygen species (mROS) support alternative regulatory T cell (Treg) differentiation.
Yet, there is little information on the impact of metabolism on innate lymphoid cells. Given the developmental and functional similarities between ILC3s and TH17, we seek to understand the molecular mechanism such as mTOR pathway that regulates ILC3 development and immunity during intestinal inflammation. Ultimately, our study may assist to identify novel avenues of therapeutic intervention based on metabolic manipulation of ILC3s in human diseases, such as inflammatory bowel disease (IBD) and colorectal cancer, where ILC3s can be inappropriately activated.