Investigating adaptive and innate immune cell interactions to better understand multi-morbidities affecting the eye and joints.

Brief Lay Background

Eye inflammation is a common condition and can happen at any age. It occurs in response to infection, allergies, irritation, injury or trauma to the eyes. But it can also happen in people who have an autoimmune condition where their immune system mistakenly starts to attack healthy tissues.

People who develop joint inflammation (arthritis) often go on to develop inflammation of the eye called uveitis, which can lead to sight loss.

What problem/knowledge gap does it help address

Previous research by Dr Gareth Jones shows that onset of arthritis causes a build-up of white blood cells in the eye. White blood cells are an important part of the immune system for fighting infection, but if they cause inflammation at the wrong time or in the wrong place it causes damage to surrounding tissue. This is what happens in uveitis and arthritis.

Finding common inflammatory processes in the two diseases could help identify new ways to treat them simultaneously, or prevent people with arthritis from going on to develop eye disease.

Dr Jones thinks that an important molecule in the immune system called interleukin-27 (IL-27) might limit arthritis and uveitis by preventing two groups of immune cells from talking to each other. It is thought that when IL-27 stops these cells communicating, it puts the brakes on inflammation and prevents the progression of disease. Now they want to determine exactly how IL-27 is related to eye inflammation, and whether preventing certain immune cells from communicating can prevent eye disease.

Aim of the research project

In this project, a PhD student will learn cutting-edge methods for understanding mechanisms behind arthritis and inflammatory eye disease in mice. The research aims to address three questions:

1. How does arthritis severity and IL-27 determine the course of eye inflammation?
2. Do immune cells that build up in the joint and eye share the same patterns of gene activity that could be targeted by treatments?
3. Does blocking communication between two distinct groups of immune cells limit uveitis in mice with arthritis?

This award will also contribute to building capacity in eye research as it will lead to a PhD for an early career researcher.

Key procedures/objectives

1. Identify which immune cells promote inflammation in the eye and joint of mice by monitoring the disease while measuring the amounts of different immune cells. They will use mice lacking the IL-27 molecule to see how this affects progression of both diseases.
2. Analyse the activity of all the different genes in immune cells using powerful single-cell genetic sequencing to see if there are shared patterns of gene activity common to both uveitis and arthritis. This could reveal potential treatment targets against both diseases.
3. Use various methods to block communication between different immune cells that are thought to drive inflammation in eye and joints in mice, and monitor the amount of immune cells that build up in the eye. This will reveal how immune cells cause sustained inflammation in the eye that ultimately leads to disease.

Potential impact on people with sight loss

This project could help to prevent or limit sight loss in people with arthritis. First, by determining how the onset of arthritis and its severity influences inflammation in the eye, it could be possible to identify early warning signs of inflammatory eye disease. Second, studying the shared inflammatory processes in arthritis and uveitis could reveal targets for new treatments that limit the course of both diseases.