Interactions between endoplasmic reticulum stress and cytokine signalling in epithelial regeneration in inflammatory bowel diseases

Publications

Epithelial RNase H2 Maintains Genome Integrity and Prevents Intestinal Tumorigenesis in Mice
ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS-STING
ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS–STING
Classic IL-6R signalling is dispensable for intestinal epithelial proliferation and repair
Epithelial IL-23R signaling licenses protective IL-22 responses in intestinal inflammation

Related News

Else Kröner Memorial Fellowship for Florian Tran
Clearly explained - Spatial Multi-Omics Phenotyping of Intestinal Tissue in Ulcerative Colitis
Berchtesgaden Microbiome Science Days 2021 – intense exchange between basic scientists, translational researchers and clinicians
Florian Tran at the 23rd United European Gastroenterology Week

Principal Investigator

Prof. Dr. med.
Philip Rosenstiel
admin1@ikmb.uni-kiel.de

Associated Principal Investigator

Dr. med.
Konrad Aden
k.aden@ikmb.uni-kiel.de
Dr. med.
Florian Tran
f.tran@ikmb.uni-kiel.de

Background and current state of research

This is the doctoral project of Dr. Florian Tran. He held a fellowship of the RTG 1743 in 2013/14.

Endoplasmic reticulum (ER) stress is an important contributor to the pathophysiology of Inflammatory Bowel Diseases (IBDs) as well as cytokines that modulate intestinal inflammation. There is growing evidence that cytokines can interact with ER stress-specific signalling pathways, e.g. via STAT1 and STAT3 phosphorylation. In particular, Interleukin (IL)-10 suppresses ER stress in goblet cells. Regeneration processes in the intestinal epithelium can also be affected by both ER stress and cytokine signalling. Intestinal stem cells lose their proliferating properties under pathological ER stress conditions whereas some interleukines promote cell cycle via STAT3 activation.

Our goals

We aim to investigate whether cytokines such as IL-10 play a modulating role for ER stress in intestinal epithelial cells in IBDs, and how cytokines and ER stress interact in regard to epithelial regeneration processes.

How to get there

Intestinal organoid derived from a small intestinal crypt from a C57BL/6J mouse, embedded in a 3D collagenous matrix; photografer: Florian Tran, IKMB

 

We will first perform in-vitro experiments that can show us the direction in which cytokines can modulate ER stress so as to investigate the cytokine-ER stress interaction. To analyze the role of this interaction in regard to epithelial regeneration, we will establish cell culture experiments as well as intestinal organoid cultures derived from primary mouse stem cells, which constitute a new tool for investigations on proliferation processes as well as a model for the gut that can be processed for cellular and molecular analysis.