Tregs: Restoring the balance in Crohn’s and Colitis

What is this research looking at?

In Crohn’s and Colitis, the immune system doesn’t work properly. The body starts attacking itself, causing ulcers and inflammation in the gut.

In this project the researchers looked at a type of white blood cell (immune cell) called Tregs. Tregs have a protective role and dampen down inflammation. Tregs have been used successfully as a treatment in animal models of Inflammatory Bowel Disease (IBD). Tregs have been shown to prevent and reverse gut inflammation in animal studies.

This research project looked at Tregs from people with Colitis and compared them with Tregs from healthy people. Finding out what role Tregs play in Colitis will help us understand whether they could be used as a future treatment option for Crohn’s and Colitis.

What did the researchers find?

In healthy people, there was a balance between the Tregs that protect against inflammation and a type of white blood cell that causes inflammation called a Th17 cell. In people with Colitis, this balance was disrupted – they had more Th17 cells (inflammatory cells) than Tregs (protective cells).

Vedolizumab treatment

The researchers also looked at people with Colitis who were taking vedolizumab. Vedolizumab is a medicine that works specifically in the gut – it stops white blood cells entering the lining of gut where they cause inflammation.

The researchers found that:

• Taking vedolizumab reduced the number of Th17 cells that were travelling to the gut.
• People who had more Tregs than Th17 cells before they started vedolizumab responded better to the treatment.

Gut bacteria

Gut bacteria play an important role how our immune system works. The researchers looked in healthy people to see if they could find a relationship between the gut bacteria a person had and their Tregs and Th17 cells.

They found that specific gut bacteria were present in people who had more Th17 cells, whereas different gut bacteria were present in people who had more Tregs.

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

• Targeting Tregs could provide a new treatment approach to reduce inflammation in people with Crohn’s and Colitis.
• Looking at Tregs and Th17 cells in the blood could be used as a tool to help decide who would respond best to vedolizumab treatment.
• Changing a person’s gut bacteria has the potential to shift the balance between the protective Tregs and the inflammatory Th17 cells. This has implications as a treatment approach for people with Crohn’s and Colitis, but also for many other inflammatory diseases where there’s a similar disruption between the inflammatory and protective cells.

Who is leading the research: Dr Nick Powell, Imperial College London
Our funding: £114,689
Duration: 24 months
Official title of the application: Regulatory T cells in IBD – optimising their therapeutic potential
Tags: Cell therapy