Role of Proinflammatory Mesenchymal Polarization in Colitis.

Mesenchymal cells are the building blocks of the connective tissue that provides rigidity and structural support for most organs. Although mesenchymal cells comprise the most abundant cell type in the intestine, their role in regulating intestinal inflammation is poorly understood. In this project we study the role of mesenchymal cells in colitis, the most prevalent form of Inflammatory Bowel Disease characterized by non-resolving inflammation in the colon tissue. Mesenchymal cells are equipped with the molecular machinery required for robust initiation of innate immune responses to a wide array of inflammatory mediators. In addition, these cells have the inherent capacity to shift between activation states in response to environmental cues and dramatically change their gene expression program and activity. We hypothesize that in the setting of colitis, mesenchymal cells are polarized by neighboring immune cells towards a proinflammatory activation state. This may lead to a vicious proinflammatory cycle perpetuated by the inflammatory crosstalk between mesenchymal and immune cells. We will first determine if the activation state of mesenchymal cells is determined by their specific interactions with immune cells. We will then determine how the crosstalk between these cells propagates proinflammatory responses in colitis.