Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) induced monocyte subsets and their potential influence on intestinal inflammation

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Recent developments in the immunology and genetics of mucosal diseases suggest that monocytes and their derivative cells play an important role in the pathophysiology of Crohn‘s disease and that blood monocytes are the exclusive source of macrophages in inflamed intestinal mucosa. Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), a hematopoietic growth factor, stimulates cells of the intestinal innate immune system. Clinical trials show that GM-CSF induces clinical response and remission in patients with active Crohn’s disease (CD). Up to date, it is still not clear how GM-CSF exerts its beneficial activities in CD, but our previous research data suggest that the GM-CSF effects could be mediated by blood monocytes. The overall aim of this project is the characterization of the immunomodulatory effects of GM-CSF treated monocytes in vivo and in vitro. We will focus on the roles of distinct monocyte and macrophage subsets in CD and aim to further characterize the phenotype of GMCSF induced specific monocyte subsets. In this regard, we will elucidate the anti-inflammatory functions of the resulting macrophage population in CD, specify the molecular machinery, and the physiological functions of GM-CSF treated monocytes and verify the effects of GM-CSF induced amelioration of experimental colitis with main focus on monocyte functions. The project could help to reveal novel insights into the pathogenesis of CD and to identify mechanisms by which modulation of innate immunity bears a potential of altering the natural history of this disease. Understanding the mechanism in CD may bear the potential of novel treatment options in the long run.