An international team of researchers led by Maynooth University scientists has new insights in to how inflammatory diseases work

 An international team of researchers, led by Professor Paul Moynagh, Head of the Department of Biology and Director of the Human Health Research Institute at Maynooth University, has made a significant breakthrough in understanding inflammatory diseases such as sepsis, Crohn’s disease, psoriasis and multiple sclerosis (MS), and identified a protein for potential therapeutic exploitation.

The scientists have discovered a protein in the body that is a key driver of inflammation. The blockade of this protein suppresses inflammation and so may offer a new approach to treating inflammatory diseases.

Inflammatory diseases are regarded as amongst some of the most difficult to treat, with sepsis in particular posing a critical challenge to frontline health care professionals. According to research by the Health Service Executive (HSE) in 2016, sepsis occurs in only 3.4% of hospital cases but contributes to 25% of all hospital deaths. This points to a clear need for effective treatment for vulnerable patients.

Professor Moynagh explains: “Inflammation is the body’s response to infection by disease-causing micro-organisms. This involves the movement of white blood cells, such as neutrophils, from blood vessels, into the infected tissue where they destroy the invading micro-organism.

“However, the recruitment of neutrophils into tissues needs to be tightly controlled since prolonged tissue infiltration of these cells will lead to damage to normal healthy tissue. In the case of sepsis, we see inflammation spread rapidly throughout the body as a response to a bacterial infection in the blood, which can lead to life-threatening organ dysfunction.”

Understanding how the body promotes the migration of neutrophils into tissue may provide important clues for designing new drugs to control chronic inflammatory diseases such as sepsis.

Prof Moynagh and his team have discovered an essential role for a protein called Pellino2 in how the body triggers inflammation and neutrophil movement into tissue. It is through finding ways to suppress or block this protein, he says, that chronic inflammation and sepsis can be treated.

Studies suggest that vulnerability to sepsis is on the rise around the world, as more people undergo invasive procedures or take immunosuppressive drugs to treat other chronic conditions, due to both aging populations and increased access to healthcare. A global rise in resistance to antibiotics also has increased the risk of blood poisoning, driving a growth in sepsis cases.

Prof Moynagh says of the research done on Pellino2: “We have already seen success with treatment models for sepsis in the laboratory by blocking Pellino2. We have seen inflammation reduce considerably where the protein was blocked, and we believe this is the first step to developing a robust new treatment for sepsis.

“We now hope to take these findings and develop drug molecules to target Pellino2. If blocking the protein works to prevent and treat sepsis, we have every reason to believe that a similar approach can be used to help those suffering with other inflammatory diseases like Crohn’s, psoriasis and even multiple sclerosis.”

Maynooth University President, Professor Philip Nolan, commented on the breakthrough: “At Maynooth University, we tackle big and difficult questions in human health. Inflammatory disease is prevalent, problematic and difficult to treat; understanding it is one of the most important challenges in medical research today. Professor Moynagh and his team’s discovery is a vital insight, a key step forward in improving treatment and patient outcomes in a wide range of diseases.”

The research project is funded by an Investigator’s Programme Award to Professor Moynagh from Science Foundation Ireland. The findings have just been published in the highly prestigious scientific journal, Nature Communications.

Prof Moynagh’s team includes Dr Fiachra Humphries, Dr Ronan Bergin, Dr Nezira Delagic, and Dr Bingwei Wang of Maynooth University, as well as Ruaidhri Jackson, who recently joined the Yale School of Medicine as Postdoctoral Associate in Immunobiology from Maynooth. Also on the team are Dr Alice V. Dubois and Rebecca J Ingram, both of Queen’s University, Belfast, and Dr Shuo Yang of the Nanjing Medical University, China.

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