Exploring the role of platelet cells in inflammation in rheumatoid arthritis

Disease - Rheumatoid arthritis

Lead applicant - Professor Christopher Buckley

Organisation - University of Birmingham

Type of grant - Full Application Disease

Status of grant - Active

Amount of the original award - £562,394.00

Start date - 01 January 2020

Reference - 22253

Public Summary 

What are the aims of this research?

This research aims to assess how platelet molecules (tiny fragments of cells that help blood to clot) can regulate other molecules in the joint in rheumatoid arthritis. Recent work has shown that platelets not only provide fuel to start the inflammatory cascade, but they can also help stop it. This study focuses on the CLEC-2 molecule attached to platelets, and its ability to supress inflammation when it interacts with another molecule called PDPN in the joint.

Why is this research important?   

Current treatments for rheumatoid arthritis have focused almost exclusively on cells of the immune system and very little attention has been paid to cells of the clotting cascade (for example platelets) and cells that make up the joint (macrophages and fibroblasts).

This research aims to investigate how CLEC-2 (which is not normally found in the healthy joint) regulates the interactions of PDPN with the cells of the joint (fibroblasts and macrophages). Better understanding how this pathway is linked to inflammation could provide a target for new treatments for rheumatoid arthritis. Researchers believe that inflammation is initiated when PDPN attaches to fibroblasts but resolved when attached to macrophages, and that the balance between the two determines if arthritis gets better or persists. The researchers will test how CLEC-2 influences this balance using both mice models and tissue samples taken from patients with rheumatoid arthritis.

How will the findings benefit patients?   

Treatments like biological therapies, have transformed the lives of many people with rheumatoid arthritis. However they do not work for everyone, so there remains a pressing need for new effective, treatments for the condition. This research aims to identify new targets for therapies that have the potential to be much more effective against rheumatoid arthritis, focusing on the PDPN and CLEC-2 pathway.