Autoimmune diseases are among the most common disorders in young adults and are known to be affected by genetic and environmental factors like vitamin D deficiency and fatty acids. Previous research found that defective regulatory T cells can lead to autoimmune disease- specifically multiple sclerosis (MS). However, until now, their underlying molecular mechanisms have remained unknown.
In the current study, researchers set out to understand more about the molecular mechanisms underlying autoimmune disease. To do so, they used RNA sequencing to compare gene expression in patients with MS and healthy individuals. Patients with MS had increased expression of a gene called PRDM1-S, also known as BLIMP-1, which regulates immune function.
The researchers found that PRSM1-S increased expression of the salt-sensitive SGK-1 enzyme, which disrupted regulatory T-cell function. In previous work, the researchers found that high levels of salt lead to inflammation in a type of immune cell known as CD4 T cells and a loss of regulatory T cell function. This process is mediated by SGK-1.
The researchers also found overexpression of PRDM1-S in other autoimmune diseases, indicating that it may be a common characteristic of regulatory T cell dysfunction.
"These experiments reveal a key underlying mechanism for the loss of immune regulation in MS and likely other autoimmune diseases," said study author David Hafler, professor of neurology and immunobiology at Yale School of Medicine, in a press release, "They also add mechanistic insight into how Treg [regulatory T cells] dysfunction occurs in human autoimmune diseases."
"Based on these insights, we are now developing drugs that can target and decrease expression of PRDM1-S in regulatory T cells," said lead study author Tomokazu Sumida, assistant professor of neurology at Yale School of Medicine, in a press release.
"And we have initiated collaborations with other Yale researchers using novel computational methods to increase the function of regulatory T cells to develop new approaches that will work across human autoimmune diseases,” he concluded.
Sources: Science Daily, Science Translational Medicine
