Immune Cells Kept in Check from Turning Against the Body by Genetic Signal

Previous research has shown that when faced with pathogens, the immune system summons a swarm of cells made up of soldiers and peacekeepers. The peacekeeping cells tell the soldier cells to halt fighting when invaders are cleared. Without this cease-fire signal, the soldiers, known as killer T cells, continue their frenzied attack and turn on the body, causing inflammation and autoimmune disorders such as allergies, asthma, rheumatoid arthritis, multiple sclerosis and type 1 diabetes.

Now, scientists at the Salk Institute have discovered a key control mechanism on the peacekeeping cells that determine if they send a halt signal to the killer T cells. The new research, published today in Cell, could help develop treatments for autoimmune disorders as well as some types of cancer.

"We discovered a mechanism responsible for stabilizing the cells that maintain immune system balance," says senior author Ye Zheng, Salk assistant professor and holder of the Hearst Foundation Developmental Chair. "The immune system plays a huge role in chronic inflammation and if we can better understand the immune system, we can start to understand and treat many diseases."

This balance of signaling for the peacekeeping white blood cells—known as regulatory T cells ("Tregs")—is crucial to normal immune response. Aside from causing autoimmune disease by not halting the attack, Tregs can conversely send too many cease-fire signals, which causes killer T cells to ignore threatening invasions. For example, some tumors nefariously surround themselves with a high density of Tregs transmitting the cease-fire signal to protect themselves from being attacked.

"Tregs are like the surveillance system of the immune response," says Zheng. "This surveillance system is key to healthy immune reactions, but it can be kicked into overdrive or turned entirely off."

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Source-Eurekalert