Soluble factors from colonic epithelial cells contribute to gut homeostasis by modulating macrophage phenotype

Abstract

Intestinal macrophages originate from inflammatory blood monocytes which migrate to the intestine, where they differentiate into anti-inflammatory macrophages through a number of transitional stages. These macrophages typically remain hypo-responsive to commensal bacteria and food Ags in the intestine, yet also retain the ability to react to invading pathogens. In this study we examined the role of epithelial cells in inducing this intestinal macrophage phenotype. Using an in vitro system we showed that, in two-dimensional culture, epithelial cell-derived factors from a murine cell line, CMT-93, are sufficient to induce phenotypic changes in macrophages. Exposure of monocyte-derived macrophages, J774A.1, to soluble factors derived from epithelial cells, induced an altered phenotype similar to that of intestinal macrophages with decreased production of IL-12p40, IL-6 and IL-23 and expression of MHCII and CD80 following TLR ligation. Furthermore, these conditioned macrophages showed enhanced phagocytic activity in parallel with low respiratory burst and NO production, similar to the response seen in intestinal macrophages. Our findings suggest a role for colonic epithelial cells in modulation of macrophage phenotype for maintenance of gut homeostasis. Further understanding of the cell interactions that maintain homeostasis in the gut could reveal novel therapeutic strategies to restore the balance in disease.