Understanding how cells talk to each other during inflammation

What this research looked at  

This research looked at how a specific genetic variation, called ATG16L1 T300A, which is linked to Crohn's Disease, affects the behaviour of cells in the bowels. This genetic variation is known to make it harder for the body to get rid of certain germs, which can increase the chances of developing Crohn's. 

The researchers created lab-grown mini version of bowel tissue, called patient-derived organoids (PDOs). Organoids mimic what is happening in the human body where cells are interacting and talking to each other all the time. 

These organoids were created from samples of tissue, also called biopsies, taken from people with Crohn's and Colitis. They also created organoids from samples of tissue taken from people without the conditions. 

They checked if these people had the genetic variation ATG16L1 T300A. The researchers used these organoids to understand how gut and immune cells talk to each other under different conditions, for example, when certain genes are turned on or off, or when cells are exposed to bacteria during an infection. 

What the researchers found

The found that people with the genetic variation ATG16L1 T300A showed a stronger response in certain cells, especially those involved in getting rid of germs (through a process called autophagy) and inflammation. This suggests that the genetic variation influences how the bowel responds to infection and inflammation. 

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

The study demonstrated the usefulness of advanced techniques for understanding more about how different bowel cells react to various conditions.

It also highlighted the potential role of the ATG16L1 T300A genetic variation in Crohn's disease, offering insights that could lead to future treatments.

The researchers plan to continue improving their methods to learn more about how immune cells and bacteria interact with bowel tissue.

Scientific publications

A novel autophagy-defective ibd organoid model reveals increased apoptosis and altered paneth cell signalling in response to tnf-alpha and bacterial ligand stimulation using multiplexed in situ mass cytometry assays. – Digestive Disease Week 2024 presentation

Who lead this research: Professor Andrew Smith, Microbial Diseases, Eastman Dental Institute, University College London 
Our funding: £179.755 
Duration: 36 months (24 months funded by us) 
Official title of application: Investigation into the role of optineurin and autophagy in IL-1B secretion and gastrointestinal inflammation