How bacterial toxins could treat autoimmune diseases
A new paper from the lab of Dr Michelle Linterman in our Lymphocyte Signalling programme has been published today by the journal Frontiers in Immunology. The research examines the potentially beneficial effects that a toxin, produced by bacteria found in the gut, has on the immune system – the group of tissues and cells inside the body that work together to help to prevent infections.
This research, which was funded by US-based organisation Trident Pharmaceuticals, revealed that breathing in part of this toxin can lower the immune system’s response in the lungs of mice. This discovery could be adapted to treat severe allergies as well as autoimmune and inflammatory diseases, where the immune system is over active and causes damage to healthy cells.
A bacteria called Escherichia coli produces toxins that can potentially cause illness in the gut. Enterotoxin subunit B (EtxB) is a part of one of these toxins. On its own EtxB isn’t harmful to cells but researchers have previously shown that it can reduce the activity of the immune system. Dr Linterman’s team have been investigating how this happens and whether it could help to control other illnesses.
One of the greatest challenges with severe allergies can be swelling in the throat and lungs caused by the abnormal activity of the immune system, making it difficult to breathe. This response is called inflammation and it is partially caused by a group of cells from the immune system called T cells. This is why Dr Linterman’s team chose to investigate the effects of inhaling EtxB on T cells in the lungs.
What the team at the Institute have found is that EtxB has two ways to weaken the immune system and prevent T cells from causing inflammation. It can reduce the function of dendritic cells, which normally push the immune system to become more active. Whilst at the same time it promotes cells called regulatory T cells that limit the activation of T cells and so reduce inflammation.
First author on the paper, Dr Alexandre Bignon, said: “It’s interesting to see the effect that ExtB has on our immune system. It’s stopping dendritic cells from activating the immune system whilst using regulatory T cells to shut down the T cells that are already there, it’s a very effective way to stop inflammation happening.”
As the lead researcher on this study, Dr Linterman said: “This work has some great potential, EtxB could become a simple and powerful way of controlling inflammatory diseases. It’s an encouraging basis for the development of fast-acting new treatments.”
This study highlights just some of the complex relationships between cells of the immune system and how they work together to respond appropriately to potential illnesses or infections. By continuing to study how the immune system is controlled we can better understand what happens when things go wrong and find new ways to harness our body’s own defences to prevent or treat diseases.
Notes to Editors:
Bignon et al. (2017) Escherichia coli heat-labile enterotoxin B limits T cells activation by promoting immature dendritic cells and enhancing regulatory T cell function. Front. Immunol. DOI: 10.3389/fimmu.2017.00560
This research was funded by Trident Pharmaceuticals, who were not involved in the study design or collection, analysis, or interpretation of the data.
Dr Linterman is supported by funding from the Biotechnology and Biological Research Council (BBSRC)
Dr Jonathan Lawson, Babraham Institute Communications Manager
Affiliated Authors (in author order):
Alexandre Bignon, Post-doctoral Researcher (Linterman Lab), Immunology Programme, Babraham Institute
Alan Watt, Xenovium Ltd., UK
Michelle Linterman, Group Leader, Immunology Programme, Babraham Institute
About the Babraham Institute:
The Babraham Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) to undertake world-class life sciences research. It's goal is to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Research focuses on signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing.
Animal research statement:
As a publically funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The research presented here used mice kept in a ‘classic wild type mouse colony’ and ‘transgenic colonies’ within the Institute’s Animal Facility. Lymph node, spleen, bone marrow and lung samples were collected from male and female mice between 8-12 weeks of age for analysis.
All animal work was approved by the Babraham Institute Animal Welfare and Ethical Review Body, and carried out in accordance with the Animals (Scientific Procedures) Act 1986, under a UK Home Office project licence. All work was carried out to ensure we adhere to the principles of the 3Rs (reduction, refinement, replacement) in our animal research. Details of the animals used in these studies can be found in the methods section of the paper.
Please follow the link for further details of the Institute’s animal research and our animal welfare practices.