Activation and Suppression of Group 3 Innate Lymphoid Cells in the Gut. Issue 8 (August 2020) - Zhou, Wenqing
Abstract : Group 3 innate lymphoid cells (ILC3s) have emerged as master regulators of intestinal health and tissue homeostasis in mammals. Through a diverse array of cytokines and cellular interactions, ILC3s crucially orchestrate lymphoid organogenesis, promote tissue protection or regeneration, facilitate antimicrobial responses, and directly regulate adaptive immunity. Further, translational studies have found that ILC3 responses are altered in the intestine of defined patient populations with chronic infectious, inflammatory, or metabolic diseases. Therefore, it is essential to broadly understand the signals that activate, suppress, or fine-tune ILC3s in the gut. Here, we discuss recent exciting advances in this field, integrate them into our current understanding of ILC3 biology, and highlight fundamental gaps in knowledge that require additional investigation. Highlights: ILC3s are tissue-resident lymphocytes enriched in the mammalian intestine that crucially orchestrate immunity, inflammation, and tissue homeostasis. ILC3s are fundamentally altered in the intestine of individuals with inflammatory bowel disease, chronic infections, or cancer. Multiple cellular and molecular circuits promote ILC3 activation, including signals derived from microbiota, pathogens, neurons, and dietary stimuli. There has been a recent appreciation of novel pathways that fine-tune or suppress ILC3s in the gut, such as plasticity, circadian rhythm, and adaptive immunity.