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Gene discovered that regulates the immune response to infection

3 December 2012
Appeared in BioNews 684

Scientists have discovered a gene that controls the immune response against infection. The finding may help in the development of treatments for some chronic infections.

The study in mice showed that the gene Arih2 was critical to the survival of embryos. In mice with a deficiency in Arih2 that did survive beyond birth, the decrease in Arih2 enhanced their immune responses to lethal effect. The mice experienced a temporary boost in their immune systems, but eventually died as their immune systems began attacking their own cells.

Lead author Dr Marc Pellegrini at the Walter and Eliza Hall Institute of Medical Research says: 'Arih2 is responsible for the most fundamental and important decision that the immune system has to make - whether the immune response should be initiated and progressed or whether it should be switched off to avoid the development of chronic inflammation or autoimmunity'.

Dr Pellegrini notes that in chronic conditions, diseases can overwhelm our immune systems. 'During evolution, some organisms have evolved ways of exhausting our immune system to the point where the immune system just switches off, and this is what happens in HIV, hepatitis B and tuberculosis'.

The researchers hope that by controlling the activity of Arih2, these chronic infections could be successfully cleared. Co-author Dr Greg Ebert, also at the Walter and Eliza Hall Institute of Medical Research, says: 'Because Arih2 is critical for survival, we now need to look at the effect of switching off the gene for short periods of time, to see if there is a window of opportunity for promoting the immune response to clear the infection without unwanted or collateral damage or autoimmunity'.

Future work will focus on creating a drug that can temporarily 'switch off' Arih2. Developing such a drug for human use will take many years, however Dr Pellegrini is hopeful, stating that: 'It [Arih2] is probably one of the few genes and pathways that is very targetable and could lead to a drug very quickly'.

The study was published in Nature Immunology.

ARIH2 is essential for embryogenesis, and its hematopoietic deficiency causes lethal activation of the immune system
Nature Immunology |  25 November 2012
Embryo survival gene may fight range of diseases: study
Reuters UK |  26 November 2012
Scientists discover gene that decides whether to 'switch on' immune system and could control HIV
Mail Online |  27 November 2012
Survival gene may be key to controlling HIV and hepatitis
Walter and Eliza Hall Institute of Medical Research (press release) |  26 November 2012
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