The Role of Intestinal Goblet Cells in Immune Homeostasis and Inflammation
Our group identified that Goblet cells can form Goblet cell associated antigen passages (GAPs) which deliver luminal substances to the underlying immune system in the lamina propria. GAP formation is a dynamic process that is tightly regulated to appropriately guide intestinal immune responses. In the homeostatic state GAPs are critical for enforcing tolerance through the delivery of antigen and the imprinting of antigen presenting cells, which can induce the induction of new antigen specific T regulatory cells (Tregs) and can maintain pre-existing Tregs in the lamina propria. We are currently exploring a role for GAP inhibition as a mechanism to ‘arm’ the immune system to fight pathogens and how this process might go awry to potentiate inflammatory diseases.
Food Allergy and Oral Tolerance
Our lab is interested in identifying mechanisms that underlie tolerance to dietary antigens and commensal gut microbes and how this can be disrupted. These studies explore how the gut becomes the site facilitating and perpetuating inappropriate allergic responses to innocuous antigens from the diet and gut microbes and understanding how interactions between intestinal epithelial cells, immune cells, and the gut microbiota promote or prevent food allergic reactions.
Early Life Immune Microbial Interactions and Development of the Gut Immune System
The gut immune system and the gut microbiota co-develop in early life with each influencing the other. Multiple immune populations are uniquely imprinted in early life and early life perturbations of the development of the immune system can have durable effects leading to an increased incidence of disease later in life. Our lab is interested in identifying the mechanisms involved in imprinting and maintaining these unique populations with various mouse models and how the microbiota shapes these cells.
Immune and Microbe Contributions to Development of the Enteric Nervous System
The Enteric Nervous System (ENS) is a central regulator of gut physiology. ENS development begins in utero and matures in the first few weeks of life. Recent observations have lead to the growing appreciation that the gut microbiota and immune system are significant contributors to ENS development in early life, and that disruption of these processes can have lasting effects on gut physiology. We are studying the effects of early life disruption of the gut microbiota by antibiotic regimens commonly used in the Neonatal Intensive Care Unit on ENS/immune development in hopes of identifying strategies to prevent and/or correct altered ENS development in pre-term infants.