Good news!
"It’s estimated that about 10% of people in the world are affected by at least one autoimmune disease—but about 65% of those people are women. Why women are so much more likely to have their immune systems mistakenly attack their own bodies is an enduring mystery in immunology. ...
The vast majority of women, however, have an XX pair. There are lots of proteins that people [???? women] with two X chromosomes would overproduce if it weren’t for a phenomenon called X-chromosome inactivation, which involves ‘turning off’ one of the two Xs by blanketing it with a long stretch of RNA called Xist. It is this process—and alterations to it—that may underlie many autoimmune diseases.
In a new study with mice, researchers discovered that if they messed with the expression of Xist, they could reactivate genes that had been silenced and spontaneously give female mice symptoms typical of lupus, a common autoimmune disease. The findings echo work from earlier this year which found that expressing Xist in male mice, which normally don’t produce the RNA, made them as likely to develop lupus as females. Both studies suggest that Xist plays a pivotal role—and could help point researchers towards new ways to treat these often devastating conditions."
From the abstract:
"In mammals, males and females show marked differences in immune responses. Males are globally more sensitive to infectious diseases, while females are more susceptible to systemic autoimmunity. X-chromosome inactivation (XCI), the epigenetic mechanism ensuring the silencing of one X in females, may participate in these sex biases. We perturbed the expression of the trigger of XCI, the noncoding RNA Xist, in female mice. This resulted in reactivation of genes on the inactive X, including members of the Toll-like receptor 7 (TLR7) signaling pathway, in monocyte/macrophages and dendritic and B cells. Consequently, female mice spontaneously developed inflammatory signs typical of lupus, including anti–nucleic acid autoantibodies, increased frequencies of age-associated and germinal center B cells, and expansion of monocyte/macrophages and dendritic cells. Mechanistically, TLR7 signaling is dysregulated in macrophages, leading to sustained expression of target genes upon stimulation. These findings provide a direct link between maintenance of XCI and female-biased autoimmune manifestations and highlight altered XCI as a cause of autoimmunity."
Fig. 2. Aberrant X-inactivation results in overexpression of several X-linked genes associated with autoimmune conditions.
No comments:
Post a Comment