A study carried out by Eric Vivier and Sophie Ugolini at the Marseille-Luminy Centre for Immunology –in which researchers from the National Centre for Genomic Analysis (CNAG), based at the Barcelona Science Park, have taking part– has just reveal a gene in mice which, when mutated, can stimulate the immune system to help fight against tumors and viral infections. Whilst this gene was known to activate one of the body's first lines of defense (Natural Killer, or 'NK' cells), paradoxically, when deactivated it makes these NK cells hypersensitive to the warning signals sent out by diseased cells. These new data are an essential step towards understanding the operation of these key cells in the immune system, and they could provide a new therapeutic approach to fighting infection. They also suggest that the operation of NK cells must be precisely regulated to guarantee an optimum immune reaction. Details of this work are published in the 20 January 2012 issue of the journal Science (doi:10.1126/science.1215621).

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Our bodies are subject to attack by many different infectious particles (bacteria, viruses, etc.), which surround us in our everyday environment. Various immune cells are activated to fight off these attacks: the first response is from the innate immune cells1, which gradually give way to the memory B and T lymphocytes of the adaptive immune system. The Natural Killer (NK) cells are a part of this first line of defence of the organism. They can selectively kill tumour cells or cells infected by microbes whilst secreting chemical messengers known as cytokines, which stimulate and direct the response of the B and T lymphocytes.

Following the launch of a major genetics programme a few years ago, scientists succeeded in revealing a gene whose deactivation causes heightened functioning of the NK cells (see figure below). This gene, called Ncr1, contributes to the manufacture of the receptor NKp46, which is present on the surface of NK cells. Surprisingly, its role in activating the NK cells has been known for several years.

To test the therapeutic potential of their discovery, the scientists blocked the NKp46 receptor using a drug (in this case, a monoclonal antibody). As in the genetics experiments, this treatment that blocks NKp46 makes the NK cells much more effective.

The role of the Centro Nacional de Analisis Genomico in this collaborative project was the identification of the gene that was responsible for the NK phenotype. This was achieved by sequencing the entire genomes of the two mutant mice to find the one base change among the 2.5 billion bases of the mouse genomes. The expertise of the CNAG was crucial for this task. The project demonstrates the importance of combining different expertise to achieve a result of such importance to the understanding of cancer and infectious disease.