November 26, 2012
Dr. Marc Pellegrini and Dr. Greg Ebert of the Infection and Immunity Division of the Walter and Eliza Hall Institute of Medical Research, Parkville, Australia, and colleagues from the University of Toronto conducted research that discovered a gene called Arih2 that is important to the function of the immune system. The gene is essential for embryo survival and could be key to treating chronic infections such as HIV, hepatitis, and TB.
Dr. Pellegrini described Arih2, which is found in dendritic cells, as the sentinels of the immune system that play an essential role in the body's response to the presence of foreign invaders. He stated that Arih2 is responsible for the decision that the immune system makes as to whether the immune response should be initiated and progressed or whether it should be switched off to avoid development of chronic inflammation or autoimmunity. He explained that the immune system works well against many infections, but some organisms have developed ways of exhausting the immune system so that the system switches off. He listed HIV, hepatitis B, and TB as examples of organisms that counter the immune response -- exhausting T cells "which are stimulated over and over again by the infection" and then become exhausted or paralyzed. He said that with this discovery, researchers should be able to reinvigorate the immune response temporarily to boost the immune system and help clear these infections.
Dr. Ebert stated that the research team was examining the effect on the immune response of switching off Arih2 for short periods of time during chronic infections and looking at how manipulating Arih2 and associated pathways promote immunity in chronic infections. He noted that Arih2 showed promise as a drug target. The researchers state that it would take many years for the discovery to be translated into a drug that can be used by humans, but that the discovery has significant implications for manipulating the immune response to infections and suppressing chronic inflammation or autoimmunity, as researchers can target this agent to try to push immune responses in different directions, either promoting or suppressing it.
The study, "ARIH2 Is Essential for Embryogenesis, and Its Hematopoietic Deficiency Causes Lethal Activation of the Immune System," was published ahead of print in the journal Nature Immunology 2012 (doi:10.1038/ni.2478).