What kick-starts the inflammatory immune response in Ulcerative Colitis?



If new treatments could be designed to target the very early stages in the inflammatory immune response, they could help maintain remission and possibly even target disease at the onset.

Professor Jo Spencer
King’s College London

What is this research looking at? 

The symptoms of Crohn’s and Colitis are caused by damage to the gut from the over-activity of immune cells, also known as chronic (ongoing) inflammation.

Professor Spencer believes that the very early stages of the immune response are key to understanding how Ulcerative Colitis develops. These early stages take place in a special part of the body called the gut-associated lymphoid tissue (GALT). GALT is where immune cells are produced, and when given their instructions, they travel from the GALT to the gut where they cause inflammation.

During a previous research project funded by Crohn’s & Colitis UK, Professor Spencer developed a new technique to take photos of the immune cells inside the GALT. The cells were stained with coloured markers that show how they are behaving and what messages they are producing. This can tell the researchers what role the cells will play in the immune response.

The photos of these cells and coloured markers can be broken down into detailed pieces of electronic information. The researchers used this to create a dataset with millions of pieces of information about GALT in people with Ulcerative Colitis and in healthy controls.

Although the GALT samples were stained with the same set of markers, these markers showed up differently in people with Colitis compared to healthy controls – indicating something different was happening with the immune response.

The current research project will bring together mathematicians and human tissue specialists to carry out an in-depth analysis on this dataset. This will tell us what is happening in the GALT in Colitis. The researchers hope to find out why so many immune cells are being produced, how they are interacting with each other and why they behave differently to the healthy controls. This will help to explain why these immune cells go on to cause damaging chronic inflammation in the gut in people with Colitis.

What do researchers think this could mean for people with Crohn's or Colitis? 

It is important to know what is happening in the GALT, as this is where the immune response starts. If we know what is causing the immune cells to develop and grow in large numbers in the GALT, the next step could be to develop therapies to block this process.

This approach differs from many current treatments as these block the inflammatory immune cells after they have already been produced in large numbers.

For example, if you imagine an overflowing bath, with water spilling out onto the floor and damaging it - the water being the inflammatory immune cells, and the floor being the gut. Current treatments work by channelling the water elsewhere (vedolizumab) or by frantically mopping the floor (infliximab). But, by turning the tap off you can stop the problem at the source, which is why the researchers believe this project could lead to exciting new treatment options for people with Ulcerative Colitis.

Who is leading this research: Professor Jo Spencer, King’s College London
Our funding: £64,636
Duration: 12 months
Official title of application: Aberrant intestinal inflammation induction in ulcerative colitis: analysis and validation of cutting edge datasets