Quercetin Exposure Suppresses the Inflammatory Pathway in Intestinal Organoids from Winnie Mice.

Manuela Dicarlo,Anastasia Sobolewski,Grazia Serino,Mauro Mastronardi,Marcello Chieppa,Angelo Santino,Mirella Falconi,Giulio Verna,Elisabetta Cavalcanti,Marina Liso,Antonio Lippolis,Sathuwarman Raveenthiraraj,Annamaria Sila,Gabriella Teti

doi:10.3390/ijms20225771

Abstract

Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that result, or possibly originate, from epithelial barrier defects. Intestinal organoids are a new reliable tool to investigate epithelial response in models of chronic inflammation. We produced organoids from the ulcerative colitis murine model Winnie to explore if the chronic inflammatory features observed in the parental intestine were preserved by the organoids. Furthermore, we investigated if quercetin administration to in vitro cultured organoids could suppress LPS-induced inflammation in wild-type organoids (WT-organoids) and spontaneous inflammation in ulcerative colitis organoids (UC-organoids). Our data demonstrate that small intestinal organoids obtained from Winnie mice retain the chronic intestinal inflammatory features characteristic of the parental tissue. Quercetin administration was able to suppress inflammation both in UC-organoids and in LPS-treated WT-organoids. Altogether, our data demonstrate that UC-organoids are a reliable experimental system for investigating chronic intestinal inflammation and pharmacological responses.

Highlights

Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that include Crohn’s disease (CD) and ulcerative colitis (UC), which can be discriminated based on the site of inflammation and the histological alterations in the gut wall
Increasing evidence demonstrated that dysfunctions in the intestinal epithelium, a monolayer of cells that lies on the lamina propria, play a crucial role in IBD pathogenesis [2]
Our findings suggest that the intestinal epithelium responds to quercetin exposure by suppressing the inflammatory response

Summary

Introduction

Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that include Crohn’s disease (CD) and ulcerative colitis (UC), which can be discriminated based on the site of inflammation and the histological alterations in the gut wall. Gut organoids are three-dimensional (3-D) in vitro models of the gut epithelium that can be isolated and grown from adult mucosal tissues (intestinal crypts) or by differentiation of embryonic (ESCs) or induced pluripotent stem cells (iPSC). These “mini-intestines” display a typical polarized intestinal epithelium subdivided in villus-like zones and crypt-like domains (“buds”). Mini-intestines recapitulating the complex architecture of in vivo gut epithelium have offered the opportunity to study physiological conditions (intestinal development, nutrient and/or drug absorption, etc.) and pathological disorders, including IBDs and cystic fibrosis [3,5,6]

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Results

Conclusion