Functional genomic studies of PTPN22 in mouse models of arthritis
Lead applicant - Professor Andrew Cope
Organisation - King's College London
Type of grant - Programme Grant Full application
Status of grant - Active
Amount of the original award - £1,000,000
Start date - 1 February 2014
Reference - 20525
What are the aims of this research?
People at risk of developing rheumatoid arthritis and lupus often carry genetic changes within a gene called PTPN22. This programme of work will investigate how a protein called Lyp, which is produced from the gene PTPN22, controls cell behaviour in ways that promote inflammation.
Why is this research important?
White blood cells orchestrate the immune response and have evolved to fight infection. In many autoimmune diseases, including rheumatoid arthritis, lupus and diabetes, the behaviour of these cells changes, making them more aggressive, which contributes to tissue damage. A protein called Lyp is involved in controlling the signals that activate white blood cells. Changes in the DNA sequence of PTPN22 lter the activity of Lyp, making cells more active and aggressive, however we do not currently understand how these changes contribute to disease and what other functions and types of cell are affected by this process.
This study will use a model of arthritis to investigate how alterations in the genetic sequence of PTPN22 change the immune system on a global scale, rather than just looking at individual cells and tissues. This will enable a range of different types of white blood cells and other molecules to be examined and provides the opportunity to examine what goes wrong with the immune system even before symptoms of rheumatoid arthritis develop.
How will the findings benefit patients?
Clarifying the role of PTPN22 and Lyp will improve our understanding of why autoimmune diseases such as rheumatoid arthritis and lupus develop. This knowledge could lead to the development of blood tests to identify individuals at high risk of these conditions who would be good candidates for preventative therapy, and may also enable new therapies to be produced which can normalise the function of the immune system.