Researchers help uncover potential breakthrough in treatments for inflammatory bowel disease (Crohn’s or Colitis)

RVC researchers help uncover potential breakthrough in treatments for inflammatory bowel disease (Crohn’s or Colitis)

Pathologists from the Royal Veterinary College (RVC) have been working with scientists from the Francis Crick Institute (FCI) to untangle a complex pathway that could help explain how interactions between microorganisms and the body’s immune defences lead to inflammatory bowel diseases (IBD) like Crohn’s disease and ulcerative colitis. Currently, 1 in every 123 people are living with Crohn’s or Colitis in the UK.

These incurable conditions cause excessive intestinal inflammation leading to persistent symptoms like abdominal pain and diarrhoea. The intestinal immune response to microorganisms is tightly controlled to limit inflammation, but when factors like genetic susceptibility and environmental triggers combine, this inflammation can progress and cause disease.

Dr Alejandro Suarez Bonnet, Lecturer in Comparative Pathology and Professor Simon Priestnall, Professor of Veterinary Anatomic Pathology at the RVC, led the assessment and validation of the in vivo experiments. Their paper has been recently published in Nature Immunology and builds on the now well-established strategic partnership between RVC and FCI in expert histopathological support. It is hoped this work could lead to the identification of new ways to treat inflammatory bowel disease.

Dr Alejandro Suárez-Bonnet commented:

"This publication is the product of a multidisciplinary approach with the contribution of top scientists at the Francis Crick Institute and the collaboration of RVC pathologists. As a veterinary and comparative pathologist specialist, I am very proud to say that the work I do on a daily basis helps to reveal the mechanisms of diseases in human patients. The work we perform during months, sometimes years, is fundamental to validate in vivo results which eventually leads to high impact publications such as this."

Professor Priestnall said:

"This exciting research builds on the now well-established partnership between the RVC and the Francis Crick Institute in provision of specialist histopathology expertise. We work with a large and growing number of Crick research groups to evaluate and assess in vivo models for a range of diseases from colitis and TB to cancer. The input we provide from experimental design through to reporting is often crucial for proof of in vitro concepts and ultimately publication."

Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. Mutations in the cytokine IL-10 (Interleukin 10 ) or its receptor result in IBD in children, suggesting the pathway is important in controlling intestinal inflammation. Earlier research by the same team have previously shown that two other proteins known as transcription factors, c-Maf and Blimp-1, drive the activity of the IL-10 gene in T cells.

In the current study, researchers deleted one or both proteins in T cells to understand their role in maintaining gut health. Removing these proteins was not enough to induce colitis, but when combined with an environmental trigger - infection with the bacteria Helicobacter hepaticus - IL-10 activity in T cells was reduced and inflammation progressed.

The researchers revealed that each protein was protective against inflammation in different ways beyond their action on IL-10, acting additionally through different immune pathways that impact distinct T cell activities.

The team uncovered how these pathways could be relevant in human IBD by studying data from colon biopsies of patients with IBD. There were similarities in the genes expressed in humans with IBD and the bacteria-induced inflammation resulting from an absence of either c-Maf or Blimp-1.

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  • The Royal Veterinary College (RVC) is the UK’s largest and longest established independent veterinary school and is a Member Institution of the University of London.
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