Gut's front-line role in immune system is adroitly explained

Standing up in front of 500 people and telling them about your job is tough enough

Standing up in front of 500 people and telling them about your job is tough enough. It gets even tougher, however, if your job involves trying to understand the causes of inflammatory bowel disease.

This chronic disorder was the subject of a presentation by Ms Lorraine Maher at the annual Merville Lay Seminars on the UCD campus earlier this month. She was both engaging and entertaining as she explained this difficult subject in everyday non-technical language, which is the challenge presented by the Merville seminars.

Her work is not specifically about the disease, however, but about the immune system and how it works in the gut. She studies the normal immune response in the stomach in order to understand what goes wrong with disorders such as inflammatory bowel disease.

The stomach is on the front line in terms of its role in immune response, she explained. "Your gut is constantly exposed to antigens and foreign substances. It has to be permanently armed to defend against infection."

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Central to her research is a chemical known as lipoxin, which she described as "a chemical produced by our immune cells during inflammation". "It is only made when the cells in our immune systems communicate with one another," she explained. It is made as a by-product but seems to have a key role as a natural brake that prevents the immune system from running out of control.

Her involvement with lipoxin arose because of contacts between her supervisor and Prof Hugh Brady of the Mater Hospital, who was part of the team that first characterised lipoxin in a laboratory in Boston. There has been much work on lipoxin and its role in the immune system since, but Ms Maher's study, which looks at how lipoxin influences mast cells, is original work.

Mast cells are found throughout the body and release chemicals including histamines. These cause inflammation but inflammation also promotes healing. With disorders such as inflammatory bowel disease this inflammatory process is not shut down properly however and chronic inflammation and damage occur.

HER work involved using cultures of human and rat mast cells present in stomach tissues as cell models. These living cells could be studied in their passive state and then after being challenged by substances which cause the cells to mimic processes seen during an immune response.

The substances given off by the mast cells after stimulation were measured and then after stimulation but in the presence of lipoxin. The release of chemicals was considerably reduced when lipoxin was there. "During inflammation lipoxin is in some way moderating this mast cell response," she explained.

Understanding how lipoxin works could be very valuable given the mast cells' central role in both allergic response and asthma. Hay fever, for example, is caused when the body's mast cells respond to harmless pollen by releasing massive amounts of histamine, which in turn causes the runny nose and itchy eyes typical of this disorder.

Lipoxin might provide a more natural way to control the immune response in allergies, asthma or in inflammatory bowel disease, she suggested. Such an approach would require much more research, however.

Ms Maher is now looking at how other cells in the gut, epithilial cells, respond to pro-inflammatory substances in the presence and absence of lipoxin. She has again used cell cultures as a way to study how these cells respond and to examine the substances they produce.

Her research is funded by Enterprise Ireland under its academic research programmes.