203 Small Intestinal Inflammatory Microenvironments In The Murine Model of Psoriasis

Abstract

Although gastrointestinal microbiome has been receiving attention to affect skin inflammation, changes in intestinal microenvironment remain largely unknown, particularly in psoriasis. In this study, we evaluated the changes in the skin and intestine of an imiquimod (IMQ)-induced murine model of psoriasis. In IMQ-treated mice, weight and energy intake was significantly decreased, while fecal protein and intestinal permeability was significantly increased. The composition of small intestinal microbiome was also altered with increased diversity. With IMQ-induced stimulation, IL-17-producing T cells were significantly increased in the skin. In contrast, IL-17 expression was significantly decreased with increased expression of IL-1beta, IL-6, TNF, and S100a8, and decreased intestinal tight junction molecules in small intestine. Interestingly, there was a marked decrease of eosinophils in the small intestine of IMQ-treated mice, with a significant upregulation of the eosinophil degranulation markers. The expression of tight junction and mucus molecules was significantly upregulated in the small intestine of IMQ-treated ΔdblGATA mice, in which eosinophil lineage is depleted, suggesting that the activation and degranulation of small intestinal eosinophils could affect pathogenesis of psoriatic inflammation by damaging intestinal barrier integrity.