Research Alert
News — In a published in Science Translational Medicine, a Yale-led team uncovers the molecular mechanism behind the loss of immune regulation seen in multiple sclerosis (MS).
Previous studies by researchers in the lab of , Professor of Immunobiology and of Neurology, established defective regulatory T cells as an underlying cause of autoimmune disease including multiple sclerosis.
In the new study, a team led by Hafler and , Assistant Professor of Neurology, used RNA sequencing to compare gene expression in patients with and without MS. In patients with MS, they found increased expression of a gene called PRDM1-S (primate-specific transcription factor), which is involved in regulating immune function.
“These experiments reveal a key underlying mechanism for the loss of immune regulation in MS and likely other autoimmune diseases,” said Hafler, who is also chair of Yale’s Department of Neurology. “They also add mechanistic insight into how regulatory T cell dysfunction occurs in human autoimmune diseases.”
Researchers found that PRDM1-S increased expression of the salt-sensitive enzyme SGK-1, which earlier studies have linked to inflammation in MS.
“Based on these insights, we are now developing drugs that can target and decrease expression of PRDM1-S in regulatory T cells,” Sumida said. “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.”
Other authors from the Yale lab include Matthew R. Lincoln, Alice Yi, Helen Stillwell, and Greta Leissa.
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