Researchers have mapped the immune cell interactions that occur in a tissue that lines the gut, revealing how these interactions change in people with the inflammatory bowel disease ulcerative colitis.
In a new study published in Science Immunology, scientists at King's College London looked at a type of tissue important for the immune response, called gut-associated lymphoid tissue (GALT).
GALT is located within the lining of the gut. Unlike other tissue structures in the gut lining, which act as a barrier between the trillions of bacteria in the gut and the rest of the body, GALT actively transports gut microbes into the body. By doing this, GALT activates immune responses that help to maintain a stable relationship with the beneficial gut bacteria.
Typically, when the body encounters microbes, it triggers inflammation, sending immune cells to the affected area to fight the pathogen. However, GALT behaves differently. Despite its close and consistent interaction with microbes, GALT does not become inflamed.
To understand how GALT achieves this, the team mapped the interactions and locations of immune cells in GALT. They also looked at how these interactions changed in ulcerative colitis - an inflammatory bowel disease where parts of the large bowel become swollen, inflamed and ulcerated. According to Crohn's & Colitis UK, at least 1 in every 233 people in the UK have ulcerative colitis. The condition can significantly impact quality of life. Previous research has linked GALT in the appendix to ulcerative colitis.
To build the map, the team looked at immune cells in GALT taken from samples of appendix tissue from healthy individuals and people with severe ulcerative colitis. Using specialised techniques including spatial transcriptomics and single cell RNA sequencing, they looked at what genes were 'switched on' in different immune cells, and where exactly different groups of immune cells were located within GALT.
The team then zoomed in further to look at white blood cells called B cells, which produce proteins called antibodies to help destroy pathogens.
In healthy tissue, the team saw that B cells interact with other groups of immune cells, including another type of white blood cell called T cells, in ways that have the potential to prevent inflammation. The different immune cells also existed in separate 'neighbourhoods' within the tissue, with the most interactive B cells located just under the outer layer of GALT where they would be close to microbes sampled from the gut.
However, in severe ulcerative colitis, normal immune cell interactions and locations were disrupted. B cells and T cells tended to be mixed rather than existing in separate neighbourhoods. The most interactive B cells were also displaced and found to be further away from the outer layer of the tissue, which could perhaps limit their ability to dampen the immune response against harmless food proteins or gut bacteria, the authors say.
"Our study is the first to describe how B cells regulate the immune response in GALT and how dysregulation of these behaviours may contribute to inflammatory bowel disease," said Professor Jo Spencer, Professor of Experimental Medicine and lead author of the paper.
Previous research has shown that a drug used in the treatment of ulcerative colitis targets GALT. The altered distribution of interactions in GALT that control the immune response that we see in appendix tissue from people with ulcerative colitis could help us understand better how existing treatments work and also to direct new therapies.
Professor Jo Spencer, Professor of Experimental Medicine at King's
The study highlights the importance of B cell interactions in maintaining a balanced immune response in GALT, and how disruption of these interactions could be linked to inflammatory conditions such as ulcerative colitis.
The work was supported by Wellcome.
