Many of the molecules in our body help our immune system stay healthy without overreacting to cause problems for our immune cells, such as autoimmune diseases. There’s a molecule called AIM2 that’s part of the innate immune system that fights pathogens and keeps you healthy. However, little is known about the function of AIM2 in T cell adaptive immunity, which is an immune defense against specific pathogens and health problems in our lifetime.
Now, in a new study, a research team led by Dr. Jenny Ting, Professor of genetics, University of North Carolina School of medicine, and Dr. Yisong Wan, Professor of Microbiology and immunology, found that AIM2 is very important for the normal function of regulatory T cells (Treg cells) and plays a key role in reducing autoimmune diseases. The related research results were published online in nature, and the paper title was “AIM2 in regulatory T cells restrains autoimmune diseases”.
Treg cells are an important population of adaptive immune cells, which can prevent overactive immune responses, such as those in autoimmune diseases. This study shows that the expression level of AIM2 in Treg cells of the adaptive immune system is actually much higher than that in innate immune cells.
“Our study reveals that AIM2 plays an unexpected and previously unrecognized role in Treg cells of the adaptive immune system, independent of the classic function of AIM2 in the innate immune system,” ting said.
“Given the known role of Treg cells in a range of diseases, including autoimmune diseases, inflammation, and cancer, our results will help us identify new molecular targets and develop new therapeutic strategies for debilitating and fatal diseases,” Wan added.
The normal immune response can resist pathogens and maintain biological stability through innate immune response and adaptive immune response. However, these responses need to be regulated to avoid their hyperactivity causing a range of different health problems. Different cell types and molecules play different roles in the down-regulation of innate and adaptive immunity. This study shows that AIM2 in Treg cells is one of them. Treg cells can inhibit the overactive immune response, so they are very important for the examination and balance of the immune system.
The dysfunction of Treg cells often disturbs the stability of the immune system and may lead to autoimmune diseases and inflammatory diseases. These researchers found that the expression level of AIM2 in Treg cells was much higher than that in innate immune cells in mice and humans.
“This suggests that AIM2 plays an important role in Treg cells,” said Dr. Wei Chun Chou, co-author and research assistant of the Ting laboratory. “We found that AIM2 is very important to maintain the normal function of Treg cells. Without AIM2, it cannot effectively prevent mice from developing autoimmune encephalomyelitis and inflammatory colitis.”
These two mouse models are the models of human diseases, multiple sclerosis, and colitis. “We conducted the further molecular and biochemical analysis to reveal a new cellular signaling pathway composed of protein molecules in Treg cells, namely the so-called AIM2–RACK1-PP2A-AKT pathway, which can regulate the metabolism and function of Treg cells, thereby alleviating autoimmune diseases.”
1.Wei-Chun Chou et al. AIM2 in regulatory T cells restrains autoimmune diseases. Nature, 2021, doi:10.1038/s41586-021-03231-w.