Scientists identify enzyme crucial for priming cells to combat autoimmune diseases

The research, published in Frontiers in Immunology, identifies a specific enzyme, known as PRMT5, as a key regulator of suppressive activity in a specialized population of cells.

The human immune system is remarkable, but in rare cases like aplastic anemia, it can malfunction. In such condition, immune cells, such as theTh1 cells, mistakenly attack healthy stem cells in the bone marrow, disrupting blood cell production essential for fighting infections, carrying oxygen, and preventing bleeding.

“What we want to do is to make a super-suppressive cell,” says Nidhi Jadon, graduate student in the Department of Veterinary and Animal Sciences at UMass Amherst and the paper’s lead author. “If someone is suffering from an autoimmune disorder, we can use these super-suppressive cells to dampen the aberrant immune response instead of drugs.”

Lisa M. Minter, a professor at UMass Amherst, developed an innovative mouse model to simulate human immune responses seen in aplastic anemia. This model featured engineered Th1 cells, inducing the disorder, focusing on training iTregs, cells responsible for suppressing the immune response, within the unique chemical environment Th1 cells create. Th1 cells utilize this environment to summon reinforcements, exacerbating the attack on bone marrow stem cells.

The findings revealed that the iTregs were very effective at reducing the Th1-mediated immune response in the animal model of aplastic anemia. After close observation, it was discovered that iTregs trained in the Th1-like chemical environment increased production of a specific enzyme, called PRMT5, which, in turn blocked the expression of another specific gene—Sirt1—that destabilizes iTregs and makes them less effective.

“No one before us has shown that PRMT5 plays such an important role in mediating the immune suppressive capacity that iTregs display, when they are generated under conditions found in a Th1-mediated immune response,” says Minter. “We’re one step closer to finding that super-suppressive cell that can replace drug therapies.”

Reference: Frontiers in Immunology; DOI:10.3389/fimmu.2023.1292049