Scientists have used information collected from a unique group of Scottish patients to uncover a new way to modify the body’s immune response which could lead to targeted treatments to reduce inflammation in diseases including arthritis and severe COVID.

The discovery came as part of a large research project between the Universities of Aberdeen, Glasgow and Exeter which focuses on how immune cells respond in different environments.

Published in Nature and funded by the Medical Research Council, Wellcome Trust, and Versus Arthirits, the study revealed that ‘finely balanced’ responses can be triggered to protect against disease and infection.

Researchers found that these responses can also reduce and prevent cell-damaging inflammation.

By investigating how the surrounding environment impacts the immune response, the team were able to pinpoint the behaviour of a key immune system receptor known as MICL.

While most receptors in the immune system respond to their environment by triggering changes that help tackle infection or tissue damage, MICL does the opposite.

The joint research revealed that this receptor actually inhibits the activation of particular immune cells.

Researchers explained that this is an important role because the over-activation of cells damage the body and even lead to autoimmune diseases if left unchecked.

An exciting breakthrough

Professor Cosimo De Bari, an academic rheumatologist from the University of Aberdeen’s Centre for Arthritis and Musculoskeletal Health involved in the study, said:

“We have discovered an important mechanism that worsens autoimmune diseases such as rheumatoid arthritis and lupus.

"This exciting breakthrough significantly advances our understanding of these and other immune-mediated diseases and may lead to novel therapies in the future.”

The researchers also investigated how modifying this response can be used to support arthritis and severe COVID patients.

The team confirmed the essential role played by the MICL receptor in regulating inflammation in some autoimmune diseases using samples from mice and patients.

Dr Mariano Malamud from the University of Exeter, and project co-lead, said:

“We’ve discovered that MICL is a key receptor that causes severe inflammatory disease when its functions are altered.

“This opens the door to the development of new therapies that target MICL, which could reduce the severity of inflammatory diseases and protect against infection.”

Researchers explored how the receptor influences the body’s most abundant immune cells which are often seen to undergo cell death in people with autoimmune diseases or infection.

They found that this receptor can both detect the cell death and act to prevent more immune cells suffering the same fate – a vital intervention for inflammatory conditions.

The team showed that when its functions are altered by antibodies, it becomes unable to prevent this cell death – resulting in more severe cases of such inflammatory conditions.

More severe disease was seen in arthritis patients who possessed antibodies targeting MICL, with these patients’ antibodies driving the exacerbated inflammatory response.

The team went on to demonstrate the essential role that MICL plays in regulating inflammation in severe COVID-19, as well as arthritis and some other autoimmune diseases.

The study also suggests that the role of this receptor in a patient’s immune system could be part of the pathways that lead individuals to develop rheumatoid arthritis in the first place.

Made possible by Scottish patients

Professor Iain McInnes, study co-author and Head of the University of Glasgow’s College of Medical, Veterinary & Life Sciences at, said that patients involved in a long-running Scottish programme played an important role:

“This study provides a vital new clue that can guide us in our search for the pathways that lead to the development of rheumatoid arthritis and other immune diseases.

“The study makes use of the Scottish Early Rheumatoid Arthritis Cohort which is a Scotland-wide effort on the part of NHS and academic consultants and most importantly our patients, to gather information and samples from people in the early years after they developed rheumatoid arthritis and thereby allow us to better understand the disease.

“Further studies are now necessary to understand how best we can capitalise on this to improve treatments in future.”

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