Investigating the role of regulatory T cells in autoimmunity

Disease - Juvenile idiopathic arthritis

Lead applicant - Dr Anne Pesenacker

Organisation - University College London

Type of grant - Career Development Fellowship

Status of grant - Active

Amount of the original award - £504,794.84

Start date - 1 July 2018

Reference - 21738

Public Summary

What are the aims of this research?

In healthy people, a type of immune cell called regulatory T cells keep the immune system balanced and stop cells from attacking our own tissues. In autoimmune diseases, this system stops working properly, but why this happens is not understood. The researchers will try to understand what happens to our regulatory T cells in autoimmune diseases.

Why is this research important?

Many juvenile idiopathic arthritis (JIA) and autoimmune patients do not respond to treatment, and therefore new drug targets are needed. Regulatory T cells receive a balance of stimulatory and inhibitory signals from co-receptors. These co-receptors could be promising targets for new drugs for autoimmune conditions. The researchers found that regulatory T cells in inflamed joints are commonly bound to a specific co-receptor pair, but the function of these receptors is unclear. Therefore, using blood cells from healthy people, and genetic engineering, they will investigate what this receptor pair does on healthy regulatory T cells, and then ask how this is changed in autoimmunity.

Regulatory T cells taken from blood and synovial fluid from patients with JIA will be studied. In addition, the researchers will look for genetic changes in patients with an autoimmune condition that has a genetic cause, and test how those genetic changes affect regulatory T cell function. Finally, the researchers will try to rescue regulatory T cells that are not working properly, this will show whether they are able to target these co-receptors to restore immune-balance and eventually develop better treatment options.

How will the findings benefit patients?

This research will show if it is possible to use co-receptors as new drug targets for JIA and autoimmunity. Ultimately, a better understanding of why regulatory T cells fail in JIA and autoimmunity will help to transform the lives of patients. By understanding the underlying mechanisms of autoimmunity, the translation of new treatments into JIA and other rheumatologic diseases could be accelerated, so that more patients can achieve remission.