AsianScientist (Nov. 27, 2012) – A gene that is essential for embryo survival could also be the key to treating chronic infections such as HIV.
The gene, called Arih2, is an E3 ligase protein that is fundamental to the function of the immune system, making critical decisions about whether to switch on the immune response to an infection.
Researchers from The Walter and Eliza Hall Institute (WEHI) in Australia collaborated with researchers from the University of Toronto, Canada on this study, which was published this week in the journal Nature Immunology.
WEHI infectious disease specialist and researcher Dr. Marc Pellegrini said that Arih2 is found in dendritic cells, the sentinels of the immune system that play an essential role in raising the alarm about the presence of foreign invaders in the body.
But while our immune system works well against many infections, chronic overwhelming infections such as HIV ‘exhaust’ and switch off the immune system, similar to autoimmune diseases such as rheumatoid arthritis and sepsis.
“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,” said Pellegrini.
“These organisms counter the immune response – exhausting T cells which are stimulated over and over again by the infection and becoming exhausted or paralyzed.”
In the study, mice that were deficient in ARIH2 died before birth (embryonic lethal). Some of the mice with a mixed genetic background survived to birth but succumbed to an aggressive multi-organ inflammatory response.
Hence, the team is now looking at the effect on the immune response of switching off Arih2 for short periods of time during chronic infections.
“This discovery has significant implications for manipulating the immune response to infections and suppressing chronic inflammation or autoimmunity because we can target this gene to try to push immune responses in one or other direction – either promoting it or suppressing it,” Pellegrini said.
The article can be found at: Lin AE et al. (2012) ARIH2 is essential for embryogenesis, and its hematopoietic deficiency causes lethal activation of the immune system.
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Source: WEHI; Photo: Ice Blade/Flickr/CC.
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