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Galectin-3 as a link between joint disease and lung dysfunction in inflammatory arthritis

Code: BC-DTP_2026_14

Title: Galectin-3 as a link between joint disease and lung dysfunction in inflammatory arthritis

Primary Supervisor: Dr Dianne Cooper

Email: d.cooper@qmul.ac.uk

Institute: William Harvey Research Institute

Secondary Supervisor: Alessandra Nerviani

Email: a.nerviani@qmul.ac.uk

Institute: William Harvey Research Institute

Lay Summary:

Inflammatory arthritis is an umbrella term that includes several conditions characterised by inflamed, painful joints, such as rheumatoid arthritis and psoriatic arthritis. These conditions significantly reduce quality of life. What is less widely appreciated is that inflammatory arthritis also increases the risk of developing problems in organs outside the joints. One important example is the lungs: lung disease is the second leading cause of death in people with inflammatory arthritis, after heart disease. Despite this, the reasons why joint disease increases susceptibility to lung disease are not well understood, and no targeted therapies currently exist.

In our work, we have identified a mouse model of inflammatory arthritis in which the animals not only develop joint inflammation but also show reduced lung function. These mice exhibit high numbers of white blood cells within lung tissue, and these cells contain elevated levels of a protein called Galectin‑3. Increased Galectin‑3 is also detectable in the blood. Galectin‑3 is known to be associated with inflammation and lung disease, and we hypothesise that it may act as a biological link between joint and lung pathology.

This project aims to investigate the role of Galectin‑3 in this process. We will examine where the protein is located and how it functions in our mouse model of inflammatory arthritis, and we will analyse Galectin‑3 levels in white blood cells from patients with inflammatory arthritis. Importantly, drugs that block Galectin‑3 are already in clinical trials for other conditions. We will therefore test these compounds in our mouse model to determine whether they can improve lung disease associated with inflammatory arthritis.

Aims:

This scheme of work aims to address an unmet clinical need by investigating the pathogenesis of lung disease in the context of inflammatory arthritis to enable earlier identification of at-risk patients for follow up and intervention. A better understanding of the mechanisms driving disease will open new therapeutic strategies as current regimens do not significantly alter patient survival (9).  Our aims are designed to characterize the link between the systemic inflammation associated with inflammatory arthritis and alterations in lung structure and function that lead to lung disease. We will characterise the pathology in our murine model of inflammatory arthritis and perform complimentary analyses with human patient samples. These experiments will provide insight into the phenotype of gal-3 expressing neutrophils as well as mechanistic insight into regulation of gal-3 expression. 

  1. Define the temporal changes in lung compliance, inflammation and fibrosis in arthritic mice.

Objectives: 

  • Determine the time course of development of reduced lung compliance in KBxN F1 mice and assess lung structure histologically at defined time-points.
  • Monitor numbers of gal-3 positive neutrophils in the circulation, lungs and bronchoalveolar lavage fluid of KBxN F1 mice over time.
  • Assess soluble mediators within bronchoalveolar lavage fluid.
  1. Characterise myeloid cell phenotype in patients with inflammatory arthritis.

Objectives:

  • Quantify levels of gal-3 in the plasma of patients with inflammatory arthritis.
  • Determine the phenotype of myeloid cells from patients with inflammatory arthritis.
  • Determine the impact of transmigration on gal-3 expression in neutrophils.
  1. Investigate the efficacy of an anti-galectin-3 therapeutic on lung compliance and inflammation.

Objectives:

  • Treat mice with a galectin-3 inhibitor to determine the effect on lung structure and function as well as circulating markers of inflammation.

References:

 

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