Master gene that switches on disease-fighting cells identified

British scientists have identified the master gene, called E4bp4, that causes blood stem cells to turn into disease-fighting 'natural killer' (NK) immune cells.

The discovery, by researchers at Imperial College London and the Medical Research Council's National Institute for Medical Research, could one day help scientists boost the body's production of these frontline tumour-killing cells, creating new ways to treat cancer.

By knocking out E4bp4 in a mouse model, the researchers created the world's first animal model entirely lacking NK cells, but with all other blood cells and immune cells intact.

The breakthrough model should help solve the mystery of the role that natural killer cells play in autoimmune diseases, such as diabetes and multiple sclerosis. According to many scientists, these diseases are a result of malfunctioning NK cells that turn on the body and attack healthy cells, which cause disease instead of fighting it. They believe that clarifying NK cells' role could lead to new ways of treating these conditions.

Natural Killer cells - a type of white blood cell - are a major component of the human body's innate, quick-response immune system, providing a fast frontline defence against tumours, viruses and bacterial infections. The gene E4bp4 is the 'master gene' for NK cell production, which means it is the primary driver that causes blood stem cells in the bone marrow to differentiate into NK cells.

Led by Dr Hugh Brady, the researchers are hoping to progress with a drug treatment for cancer patients which reacts with the protein expressed by their E4bp4 gene, causing their bodies to produce a higher number of NK cells than normal, to increase the chances of successfully destroying tumours.

"If increased numbers of the patient's own blood stem cells could be coerced into differentiating into NK cells, via drug treatment, we would be able to bolster the body's cancer-fighting force, without having to deal with the problems of donor incompatibility," Nature quoted Brady as saying.

The researchers proved the pivotal role E4bp4 plays in NK production when they knocked the gene out in a mouse model.

Without E4bp4 the mouse produced no NK cells whatsoever but other types of blood cell were unaffected.

"Now finally, with our discovery of the NK cell master gene and subsequent creation of our mouse model, we will be able to find out if the progression of these diseases is impeded or aided by the removal of NK cells from the equation. This will solve the often-debated question of whether NK cells are always the 'good guys', or if in certain circumstances they cause more harm than good," said Brady.

The study has been published in Nature Immunology.