William O'Connor Jr, PhD

In the gastrointestinal tract, immune sensing of luminal content influences resident microbial communities, and the microbiota in turn educate cells of the immune system.  These events drive powerful immune and inflammatory processes locally and in distal organ systems.  The level of coordination and extent of signal integration in determining inflammatory outcomes in the GI is remarkable. Signals derived from resident and infiltrating immune cells, stromal cells, and the commensal microbiota all contribute, and most of this signal integration remains poorly understood.

Our long-term goal is to understand how inflammation and mucosal healing are controlled. Improper immunoregulation at the mucosa is thought to drive a number of inflammatory disorders, including the inflammatory bowel diseases (IBDs), and may facilitate the progression to neoplasia.

Among the myriad of soluble factors controlling the initiating and resolving phases of inflammatory processes are cytokines, which participate in both pro-inflammatory signaling as well as in mucosal healing.  Cytokines are generally pleotrophic and function in a microenvironment- and context-specific fashion.  In the intestine, cytokines may be pro-inflammatory, anti-inflammatory, or 'inflammation-neutral'.  Th17-associated cytokines are of particular interest, modulating immune cell recruitment, antimicrobial host defense, and tissue-protective processes.  Cytokine function and integrated responses are a recurring theme in our research and are long-standing interests. We are currently investigating several novel mechanisms governing inflammation and mucosal healing in the GI tract.