Summaries of 2025 research

What animals are you planning to use?

Mice.

For what purpose are the animals going to be used?

Inflammation is the body's response to infection or injury and contributes to the healing process. In rheumatoid arthritis, appropriate control of inflammation is lost promoting joint disease. Importantly, the pattern of joint inflammation often differs considerably in rheumatoid patients to affect the rate of disease onset, the severity and response to therapy. Studies outlined here will define the mechanisms that account for these clinical differences. ‘Inflammatory signatures’ that reflect these various forms of disease will enhance our understanding of rheumatoid arthritis in humans and will provide an opportunity to improve patient diagnosis and treatment decisions.

What will be the harms to those animals and how will these be limited?

Mice with experimental forms of arthritis develop joint inflammation and show signs of joint disease (e.g., swollen joints that restrict their mobility) and some changes in pain. To limit the impact of our work, we primarily use model systems that affect one knee joint. Where appropriate, we use historical datasets and data available in open access repositories to reduce and refine our experimental designs. Over the last 5-6 years, we have also adopted technologies that allow us to generate more information using fewer animals. All findings obtained from our mouse work are always related back to data from patients with rheumatoid arthritis. This approach verifies our mouse discoveries and limits our reliance on animals.

What alternatives did you consider before embarking on the use of animals in your research?

Our mouse studies are complimented by experiments performed using human cells, and joint tissue biopsies and other clinical samples from patients in clinical trials. This approach ensures that our animal studies appropriately reflect human disease. However, animals are required to understand the mechanisms driving disease. Here, it is often difficult to distinguish factors that cause disease versus those that are simply produced as a consequence of the disease. Animal models, therefore, provide us with the means to understand the complexity of cell-to-cell communication within the inflamed joint.

Clues as to how arthritis develops reside in the pre-clinical stage (where symptoms may not be apparent to the patient) of the disease. Unfortunately, this phase of human arthritis is not readily accessible to investigation and any interpretations are often speculative. By combining studies in humans and mice we are able to distinguish key processes affecting disease severity and the response to therapy.

What will be the expected benefits?

Our long-term objective is to aid patient diagnosis, treatment, and cure by identifying the processes that dictate the course of joint disease and multimorbidity in arthritis. Adopting animal models of inflammatory arthritis that mimic the heterogeneity of human disease, our investigations are revealing the mechanisms that direct the pattern and severity of disease and the response to therapy.