TLR-independent anti-inflammatory function of intestinal epithelial TRAF6 signalling prevents DSS-induced colitis in mice

Gut
Katerina VlantisAndy Wullaert

Abstract

The gut microbiota modulates host susceptibility to intestinal inflammation, but the cell types and the signalling pathways orchestrating this bacterial regulation of intestinal homeostasis remain poorly understood. Here, we investigated the function of intestinal epithelial toll-like receptor (TLR) responses in the dextran sodium sulfate (DSS)-induced mouse model of colitis. We applied an in vivo genetic approach allowing intestinal epithelial cell (IEC)-specific deletion of the critical TLR signalling adaptors, MyD88 and/or TIR-domain-containing adapter-inducing interferon-β (TRIF), as well as the downstream ubiquitin ligase TRAF6 in order to reveal the IEC-intrinsic function of these TLR signalling molecules during DSS colitis. Mice lacking TRAF6 in IECs showed exacerbated DSS-induced inflammatory responses that ensued in the development of chronic colon inflammation. Antibiotic pretreatment abolished the increased DSS susceptibility of these mice, showing that epithelial TRAF6 signalling pathways prevent the gut microbiota from driving excessive colitis. However, in contrast to epithelial TRAF6 deletion, blocking epithelial TLR signalling by simultaneous deletion of MyD88 and TRIF specifically in IECs did not affect DSS-ind...Continue Reading

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Citations

Mar 1, 2016·Frontiers in Immunology·Aline IgnacioRafael Ribeiro Almeida
Oct 1, 2015·Journal of Crohn's & Colitis·Edel McDermottTherese M Murphy
Mar 22, 2016·International Journal of Medical Microbiology : IJMM·Claudia GüntherJan Wehkamp
Jul 31, 2016·Biochemical and Biophysical Research Communications·Haihua RuanJian-Jun Qiao
Mar 24, 2018·Viruses·Rebecca N MetzgerKatharina Eisenächer
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Jul 8, 2016·Nature·Christoph A ThaissEran Elinav
Mar 13, 2018·Current Pharmacology Reports·Almin I LalaniPing Xie
Mar 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Xinghua GaoYong Yang
May 17, 2018·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Qin ZhaoXiuli Zuo
Oct 9, 2018·Frontiers in Immunology·Sining ZhuPing Xie
Aug 10, 2018·JCI Insight·Reiko MatsumotoKenji Kabashima
Feb 26, 2021·The Journal of Microbiology·Rutao LinYaoxing Chen
Apr 12, 2021·Biochemical and Biophysical Research Communications·Lifen ZhaoShufen Li
Jul 10, 2021·European Journal of Immunology·Timur Tuganbaev, Kenya Honda
Oct 10, 2021·Nature Communications·Hannah SchünkeManolis Pasparakis

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Methods Mentioned

BETA
IECs
transgenics
IEC
electrophoresis

Software Mentioned

Excel

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