A newly discovered ‘Goldilocks’ protein may be responsible for helping keep the immune system from running amok, according to researchers at the Lunenfeld-Tanenbaum Research Institute (LTRI).
This protein, known as WAVE2, is expressed in all immune cells and plays a critical role in keeping the immune system in balance. To test its role, researchers knocked out the WAVE2 protein in a subset of immune cells in mice, leading to severe autoimmunity and inflammation, as well as an inability to mount an immune response to a viral infection.
Senior author Dr Kathy Siminovitch, said the team also found that in the absence of WAVE2, another protein, known as mTOR, became overly active, sending the immune system into overdrive and leading to immune cell exhaustion.
“Much like Goldilocks, a proper immune response requires such a delicate balance,” said Dr Siminovitch. “You have to get it just right. By developing a mouse strain in which T cells, key players in immunity, lack WAVE2, we have shown that this protein is absolutely required for balanced immune responses.”
The question of how to keep the immune system in balance is of key importance in the pandemic, where many deaths occur due to cytokine storms as the immune system overreacts, especially in the elderly.
As part of her work exploring the mechanisms balancing the immune system, Dr Siminovitch helped trace the complex molecular steps that turn a rare gene mutation into Wiskott-Aldrich syndrome, a potentially lethal disease which impairs the immune system of boys.
Future research would look at how the contribution of the WAVE2-mTOR pathway to specific autoimmune, inflammatory and other conditions, such as Alzheimer’s disease.
Source: News-Medical.Net
Journal information: Liu, M., et al. (2021) WAVE2 suppresses mTOR activation to maintain T cell homeostasis and prevent autoimmunity. Science. doi.org10.1126/science.aaz4544.
