Scientists discover new player in immune system

An international team of scientists has discovered a new player in the immune system of fruit flies, mice and humans, called Akirin (Japanese for ‘making things clear’), the molecule plays an
important role in triggering the innate immune response.

The scientists, from France, Germany and Japan, publish their findings in the journal Nature Immunology.

The innate immune system is found in all animals. When receptors on the surface of cells recognise an invader, they send a message into the cell’s interior. The cell then releases
immunologically active proteins. The innate immune system has changed little throughout evolution, and many of the molecules involved in the fruit fly’s innate immune system can also be found
in our own.

Vertebrates also have an acquired immune system. This additional layer of defence involves antigens that enable the body to ‘remember’ pathogens it has encountered. If the pathogen attempts to
infect the body again, these ‘memory’ antigens are able to mount a speedy and effective response.

Because they lack an acquired immune system, fruit flies are often used to study the innate immune system. In fruit flies, there are two signalling pathways which can be triggered when the
immune system detects an invader. One of these is called ‘Imd’ (for immune deficiency), and although it was discovered over 10 years ago, this pathway is still not fully understood.

In this latest study, the scientists used RNA interference (RNAi) to switch off individual molecules in the pathway. This experiment threw up a previously unknown molecule, which they baptised
Akirin.

When Akirin was switched off in the immune cells of the flies, they became significantly more susceptible to bacterial infections. If the molecule was blocked throughout the body, the flies
died early on in the larval phase.

Further studies revealed that the mouse version of Akirin plays a similar role to the fly version. In addition to this, when the human version of Akirin was produced in flies whose own Akirin
had been blocked, the innate immune response was restored.

The findings could lead, one day, to the development of new cancer treatments. ‘What is called the NF-fÛB signalling pathway plays an important role in inflammations, and inflammations
are highly relevant in cancer development,’ explained Michael Boutros of the German Cancer Research Centre (DKFZ), one of the authors of the paper. ‘Therefore, the search is on for small
molecules that can inhibit this signalling pathway.’

Drugs designed to block other links in the signalling chain are already being tested in clinical trials. ‘The more links of this chain we know, the more possibilities we have to interfere with
it,’ said Dr Boutros.

For more information, please visit:
https://www.nature.com/natureimmunology
https://www.dkfz.de