Dr. Manu Rangachari and his research team at Université Laval have identified a new mechanism for sex differences in multiple sclerosis (MS). While biological sex is well recognized as an important determinant of MS incidence, with women being 2-3 times more likely to develop MS than men, what remains unclear is why MS in men tends to progress more rapidly and aggressively.
By developing a mouse model with MS-like disease, Dr. Rangachari and team discovered that immune cells (T cells, specifically Th17 cells) from male mice are more pathogenic compared to females, causing a more severe and progressive disease in males. They showed that the enhanced pathogenicity of male T cells may be a result of decreased expression of a gene called Jarid1c, an immune regulator gene in the X chromosome capable of reducing the ability of T cells to induce MS-like symptoms in mice. The team also confirmed that T cells from people with MS have low levels of Jarid1c, particularly T cells collected from male patients compared to females. These results suggest that Jarid1c may play a role in regulating T cell activity in a sex-dependent manner in MS.
This study represents an important advancement in our understanding of how biological sex can act as a determinant of disease severity in MS. Additional research is needed to understand the role of Jarid1c gene in modulating MS severity and how it could be used as a potential drug target for MS therapies.
The study was published in Cell Reports – link. To learn more about this exciting research, please refer to the following video.