Skin based immunity secrets revealed

A team of international scientists have discovered a new mechanism by which immune cells in the skin act as the body’s ‘border control’, revealing how these cells sense whether lipid...

A team of international scientists have discovered a new mechanism by which immune cells in the skin act as the body’s ‘border control’, revealing how these cells sense whether lipid or fat-like molecules might indicate the presence of foreign invaders. 

The findings published today in Nature Immunology could improve how we fight some infections, allergies and autoimmune diseases.

The discovery by researchers from Monash University, the University of Melbourne and Harvard University is a fundamental advance in understanding how the immune system functions, particularly within the skin.

Human skin contains an extensive network of immune cells that act as a crucial barrier to infection, but when these immune cells recognise the body’s cells or foods as foreign, they can have unwanted side effects, such as inflammation and allergies.

One molecule, termed CD1a, found on these skin based immune cells, plays a key role in this response, by binding to, and displaying, foreign lipid (or fat-like) molecules derived from bacteria, and also lipids from our own cells, for recognition by T lymphocytes within our immune system.

The CD1a molecule behaves as border control staff reading the lipid molecules which act like passports to identify which compounds belong to the body or not.

It is this interaction that has been unravelled by the teams of Professor Jamie Rossjohn, Monash University, Professor Dale Godfrey at the University of Melbourne, and Professor Branch Moody from Harvard University.

Even though CD1a was discovered over 30 years ago, and it is known to be involved in immunity to mycobacteria and inflammation following bee stings, how the immune system interacted with these CD1a molecules has been a mystery.

Professor Godfrey said lipids were potent stimulators of the immune response and they were produced by pathogens, allergens and our own cells.

"This work shows that the means by which the immune system detects lipids is very different to the mechanism underlying recognition of proteins,” Professor Godfrey said.

Professors Rossjohn and Godfrey, in conjunction with the Australian synchrotron, provided detailed molecular insight into how the immune system engages with complexes of CD1a and lipid molecules.

They defined a completely novel mechanism of immune cell recognition and provided valuable insight into how this part of the immune system operates and how it might be manipulated as a means for enhancing immunity to infection or suppressing immunity associated with allergic reactions.

Professor Rossjohn said: "By understanding how the human immune system can sense and respond to lipids, we can make them more or less potent by subtly altering their structure."

The research was supported by the National Health and Medical Research Council of Australia, the Australian Research Council, the National Institutes of Health and the Dermatology Foundation.