Discovery of the master gene behind the front-line troops of the body鈥檚 immune system could promise a host of new treatments for disease. Called E4BP4, the gene kick-starts production of natural killer (NK) cells in the bone marrow.
Mice genetically engineered to lack the gene were able to make all other components of the immune system 鈥� such as B cells which produce antibodies and T cells which attack pre-selected targets 鈥� but not NK cells. This suggests that E4BP4 is indispensable for their production. 鈥淣ow we know which gene is at the top of the hierarchy, it opens the door to the whole machinery for making them,鈥� says of Imperial College London.
Brady and colleagues hope it may now be possible to develop drugs that artificially boost production of NK cells, helping patients to combat infections or cancer. Patrolling the bloodstream, the spleen and the lymph nodes, NK cells are the body鈥檚 first line of defence against disease, rapidly identifying and destroying cells that have turned cancerous or been invaded by viruses.
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Less well studied than B and T cells, NK cells account for about a fifth of all the body鈥檚 white blood cells. 鈥淭hey鈥檙e very much the cinderellas of the blood system,鈥� says Brady. 鈥淏ut if you get an infection, these are the guys who get there first, and they鈥檙e the first line of tumour immunosurveillance.鈥�
Treatment hope
Now that a mouse incapable of making NK cells is available, it will be possible to mount experiments that reveal exactly what they can and can鈥檛 do, says Brady. And with that knowledge, it might be possible to develop new treatment鈥檚 to boost NK cell activity, or other components of the immune system.
鈥淭his is an exciting discovery that could open the doors for new ways to treat cancer in the future,鈥� says Josephine Querido, senior information officer at Cancer Research UK. 鈥淥ur immune system is an immensely powerful weapon in helping the body to fight disease, and this research helps to explain how a crucial part of these defences work.鈥�
The other intriguing finding, says Brady, is that although mice couldn鈥檛 make NK cells if they lacked two copies of the E4BP4 gene (one from each parent), they did made half the usual number of NK cells if they had one copy of the gene. If the same is true in humans, it may explain why some people are unusually prone to infection or cancer.
Journal reference: Nature Immunology, DOI: 10.1038/ni.1787
