Z Gastroenterol 2014; 52 - FV10
DOI: 10.1055/s-0034-1385984

The epithelial IL-23R mediates intestinal immune defense and epithelial regeneration

K Aden 1, A Rehman 1, R Häsler 1, F Tran 1, S Pfeuffer 1, S Billmann 1, M Paulsen 1, S Lipinski 1, A Kaser 2, S Schreiber 1, P Rosenstiel 1
  • 1Institut für klinische Molekularbiologie, Kiel, Germany
  • 2University of Cambridge, Division of Gastroenterology and Hepatology, Department of Medicine, Cambridge, Germany

Background and aims: The identification of the IL23R as a genetic risc factor in inflammatory bowel disease (IBD) has highlighted the role of IL-23 signaling in the intestinal immune response. However, the impact of IL-23 on the immune regulation is ambigious. Whereas IL-23 induced Th-17 polarization contributes to pathogenesis of IBD5, IL-23 induced IL-22 in Thy-1+ innate lymphoid cells is indispensable in the innate immune response to bacterial pathogens and experimental colitis. This study aimed to describe the role of the Il23R in the intestinal epithelium.

Methods: Conditional knockout of the Il23R in the intestinal epithelium was established by crossing VillinCre mice with Il23Rfl/fl mice, resulting in IL23RIEC-KO or IL23Rfl.

For chronic colitis induction, mice were supplied with 2% of DSS dissolved in drinking water for 5 days followed by 5 days of regular drinking water with total 3 cycle repetitions.

Diseased intestines were subjected to gene expression analysis was performed using custom made TaqMan probes and post-mortem histopathological analysis.

Lumina faeces were subjected to pyrosequencing of bacterial DNA and sequences with at least 97% similarity were clustered in to species level operational taxonomical units (OTUs).

Results: Here we show that IL23R is expressed in intestinal epithelial cells and profoundly affects the intestinal immune defense. IL23RIEC- KO mice produce less antimicrobial peptides, have a disturbed colonic microflora and succumb to experimental colitis. IL23RIEC- KO intestinal lamina propria cells contain less immune cells and produce less IL-22 in response to IL-23 or Flagellin stimulation. Lastly, we could show, that IL-22 therapy fully restores epithelial immune defense in IL23RIEC- KO.

Conclusions: These data contribute to the understanding of the IL-23 axis in primary immune response and describes a so far unknown role of IL23R signaling in the intestinal epithelium.

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