Our research focuses on how immune cells integrate multiple signals to maintain homeostasis within their resident tissues. In many cases, this molecular dialogue is initiated by epithelial cells and innate lymphoid cells (ILCs), which produce hallmark cytokines that reflect subsequent adaptive immune responses mediated by T cells. We are interested in how ILC- and T cell-derived cytokines amplify normal tissue functions to maintain organ health.

One such function is the degradation of chitin, a widespread polysaccharide and constituent of fungi, helminths and arthropods. Chitin activates a robust immune response that converges on tissue-resident lymphoid cells, particularly ILC2s, which communicate with epithelial cells via cytokines to boost production of chitinases, specialized chitin-degrading enzymes. These enzymes break down insoluble chitin, thereby relieving the immune stimulus and restoring normal tissue function. Indeed, in the absence of this feedback system, environmentally-derived chitin polymers accumulate in mammalian tissues. In the respiratory tract, chitin accumulation provokes chronic inflammation, ILC2 triggering, and can lead to tissue fibrosis and mortality. In the gastrointestinal tract, a similar immune-epithelial cell circuit governs dietary chitin digestion and nutrient extraction from chitin-containing foods. Understanding tissue-restricted cytokine feedback loops may thus inform treatment strategies for chronic inflammatory diseases associated with ill-defined tissue remodeling and regenerative pathways. We employ cutting-edge technical approaches to decode the specific signals that organize these loops in development, tissue injury, and infection to determine whether they can be manipulated to regulate barrier integrity and organ health.