Stromal Cell Subsets Show Model-Dependent Changes in Experimental Colitis and Affect Epithelial Tissue Repair and Immune Cell Activation.

Abstract

Background: Previous work on inflammatory bowel disease (IBD) revealed changes in the abundance of colonic stromal subsets during intestinal inflammation. However, it is currently unknown whether these stromal cell subset changes are also reflected in different IBD mouse models and how commonly used IBD therapies affect stromal cell subset composition.

Methods: Stromal subset markers CD55, C-X-C motif chemokine 12 (CXCL12), podoplanin (PDPN), CD90, and CD73 were analyzed by flow cytometry in 3 mouse models for IBD, namely interleukin (IL)-10 knockout (KO), dextran sulfate sodium-induced, and T-cell transfer model for colitis. Next, the effects of IBD therapies on the stromal subset composition were studied. In vitro experiments were performed to study the interaction between stromal cell subsets and epithelial/immune cells.

Results: The colitis-induced changes in the abundance of stromal cell subsets differed considerably between the 3 colitis mouse models. Interestingly, treatment with IBD medication affected specific stromal subsets in a therapy and model-specific manner. In vitro experiments showed that specific stromal subsets affected epithelial wound healing and/or T-cell activation.

Conclusions: The relative abundance changes of stromal cell subsets during experimental colitis differ between 3 established colitis models. Treatment with IBD therapies influences stromal subset abundance, indicating their importance in IBD pathogenesis, possibly through affecting epithelial migration, and T-cell activation.