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Scientists Discover Off-Switch to Regulate Immune System

  • Jessica Berman

Scientists have discovered a cellular "off-switch" that could allow doctors to control the body’s immune response in a host of diseases, and could boost the efficiency of vaccines against diseases like HIV and malaria.

The so-called "off-switch" is a protein called TMED7. Researchers at Ireland’s Trinity College Dublin say in normal, healthy cells, the protein calms the immune system after it is done fighting a bacterial infection.

Anne McGettrick co-led the study that identified TMED7. She likens the immune system to an orchestra with many different sections, and TMED7 to one of the instruments. It is the first member of a family of proteins to be identified as an important regulator of the immune system.

“Why that’s exciting to us is because the more we can tweak just small aspects of our immune system, and the more we understand about how each bit works, the more likely we are to understand what’s going wrong in diseases - why some people get different symptoms - and that when their immune system goes wrong we can work out which pathways are going wrong,” McGettrick said.

Without TMED7 acting as a brake, McGettrick says the immune system would rage out of control after neutralizing a bacterial infection.

Researchers knocked out the protein and then infected the cells with a bacterium. They found the cellular immune response became over-activated.

McGettrick believes developing drugs, or vaccine adjuvants, that crank up the immune system by removing TMD7 from cells could help boost the effectiveness of vaccines, against HIV and malaria. Vaccines work better when the body's immune system response is robust.

“That’s the next avenue that we want to go down to see if knocking out this gene is a candidate for a vaccine adjuvant,” McGettrick said.

The researchers also imaged unaltered cells, and then exposed the cells to a bacterial microbe, to see TMED7 at work.

“It allowed the immune system to work for the length of time that it needed to work and then it moved in to do its job [of stopping the immune attack],” McGettrick said.

In the case of autoimmune diseases, in which the body’s immune system goes into over-drive and attacks its own tissues, tweaking TMD7 and other immune regulators, according to McGettrick, could lead to treatments to reduce the severity of the attack.

An article by Anne McGettrick and colleagues describing discovery of the immune system off-switch protein, TMD7, is published in Nature Communications.