Researchers from China identified a potential pathway that may promote the differentiation of T helper 17 (Th17) cells in neuromyelitis optica spectrum disorder (NMOSD) following the downregulation of long noncoding RNA X inactive specific transcript (lncRNA XIST).
“These findings shed new light on the immune regulation mechanism about lncRNA XIST and related epigenetic features, which may contribute to develop[ing] female-specific treatment plans,” they wrote in a report that they published in the journal Multiple Sclerosis and Related Disorders.
Read more about the pathophysiology of NMOSD
Previous research has shown that the proportion of Th17 cells is significantly high in patients with NMOSD. It is also known that lncRNA XIST is a key regulator of X-chromosome inactivation, which is linked to sex disparity in autoimmunity.
Here, a team of researchers led by Bin Li assessed the expression levels of the lncRNA XIST-lysine demethylase 6A-T cell-specific adapter pathway in women with NMOSD and explored the potential link with NMOSD pathogenesis.
The team enrolled 30 women with acute-phase patients with NMOSD who were untreated and 30 age-matched healthy women and collected their lymphocytes.
Using microarray and validation experiments, they showed that lncRNA XIST was significantly downregulated in patients with NMOSD compared to healthy controls.
Moreover, the levels of lysine demethylase 6A decreased and showed a significant positive correlation with XIST.
The levels of T cell-specific adapter (TSAd) were also significantly lower in patients with NMOSD compared to healthy controls both at the mRNA and protein levels.
Using chromatin immunoprecipitation assay, the researchers showed that patients with NMOSD had more H3K27me3 modification, an epigenetic modification of histone 3 protein, compared to controls at the TSAd promoter region.
“The present study introduced a potential pathway that following lncRNA XIST downregulation, which process may promote Th17 differentiation in NMOSD,” they concluded.
NMOSD is a rare, autoimmune disease caused by the autoantibodies attacking aquaporin-4 channels.
Guo RY, Song S, Wang JQ, et al. Downregulation of lncRNA XIST may promote Th17 differentiation through KDM6A-TSAd pathway in neuromyelitis optica spectrum disorders. Mult Scler Relat Disord. Published online June 10, 2023. doi:10.1016/j.msard.2023.104801