Tissue Regulation of Immunity and Inflammation

EPITHELIAL cells lining the intestinal barrier constitute the first line of defense regulating immune cell reactions to commensal microbes and environmental antigens. Barrier integrity is maintained by constant secretion of mucin glycoproteins by epithelial goblet cells, generating a protective mucus layer at the interface between intestinal cells, immune cells and the gut microbiota. By genetically targeting IL-18 signaling pathway in epithelial and immune cells, we identified IL-18 as the principal driver of goblet cell dysfunction and mucus depletion in mouse models of intestinal inflammation. Our studies demonstrated that IL-18 functions early in the pathological sequence of colitis, leading to breakdown of the mucosal barrier. Our lab studies how intestinal epithelial cells coordinate the immune response in the setting of intestinal inflammation. 

MESENCHYMAL cells are engaged in close interactions with immune cells residing in the connective tissue. Akin to immune cells, mesenchymal cells respond to a wide array of immune mediators and environmental cues by producing immunomodulatory factors that can critically shape the immune response. Mesenchymal cells are in fact involved in various aspects of immune cell migration, activation and survival, underscoring the importance of this axis in regulation of immunity and inflammation. Our lab studies the cellular and molecular mechanisms governing mesenchymal-immune interactions and functional crosstalk in immunity and inflammation.

ENDOTHELIAL cells are charged with the important task of regulating immune cell infiltration from the blood to sites of infection or tissue damage. In addition to immune cell trafficking, endothelial cells function as early and potent activators of the tissue innate immune response to pathogens and microbial products, failure of which is associated with the pathogenesis of sepsis and organ failure. Our lab studies the endothelial immunoregulatory pathways involved in the pathogenesis of local and systemic inflammation.