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Background

Inflammation, injury, and infection upregulate intestinal expression of the tryptophan metabolizing enzyme indoleamine 2, 3-dioxygenase 1 (IDO1). In most disease models, IDO1 activity dampens inflammatory responses, reduces host injury and promotes recovery. Although epithelial cells are the predominant source of IDO1 during intestinal inflammation recovery and repair, the specific role of epithelial IDO1 has not been examined.

Methods

We generated a novel transgenic mouse model that overexpresses EGFP-tagged IDO1 in the intestinal epithelium under the villin promoter (IDO1-TG). Using primary intestinal spheroid culture, we quantified stem cell and differentiation markers by qRT-PCR and immunofluorescence. Mucus thickness and luminal microbiota were assessed in vivo. A published database from Crohn’s disease patients were interrogated for secretory lineage genes.

Results

IDO1-TG …