Immune regulation in the gastrointestinal tract

Immune regulation in the gastrointestinal tract (Back to main page)

A large part of our published work focuses on the mechanisms that underlie mucosal regulatory T-cell (Treg) differentiation. We have shown that the microenvironment, in particular the nature of the antigen presenting cell and cofactors such as cyclooxygenase derived prostaglandins and Fc receptor mediated signaling in the intestinal draining lymphoid tissue are crucial for inducible Foxp3+ Treg differentiation. Continuous surveillance by suppressive Treg cells prevents inflammatory responses to luminal antigens thereby maintaining intestinal homeostasis. However, the nature of the antigenic pressure varies at different locations of the intestinal tract. In agreement with this strong microenvironmental control our research shows that small intestinal and colonic Treg induction and function varies considerably. This led to the discovery that, in mice disruption of IL-10-driven- signaling in antigen presenting cells leads to spontaneous inflammation in the small intestine but not the colon. However, when colonized with Helicobacter hepaticus deficiency of IL-10 signaling in antigen presenting cells causes severe colitis. Using these mouse systems and cells from an IL-10R deficient patient we now have the possibility to perform in depth analysis of how the IL-10 pathway controls inflammatory Th1 and Th17 cells in small intestine and colon.

  

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