Good news! Perhaps a breakthrough!
"... More than 24 million Americans, by some estimates up to 50 million, have an autoimmune disorder — diseases such as lupus, rheumatoid arthritis, multiple sclerosis and dozens more. About 4 of every 5 patients are women, a mystery that has baffled scientists for decades.
One theory is that the X chromosome might be a culprit. ...
The new research, published in the journal Cell, shows that extra X is involved — but in an unexpected way. ...
Every female cell must switch off one of its X chromosome copies, to avoid getting a toxic double dose of all those genes.
Performing that so-called X-chromosome inactivation is a special type of RNA called Xist ... attracts proteins that bind to it in weird clumps, and silences the chromosome. ...
identified nearly 100 of those stuck-on proteins ... many ... related to skin-related autoimmune disorders — patients can have “autoantibodies” that mistakenly attack those normal proteins. ..."
From the highlights and abstract:
"Highlights
• Transgenic mouse models inducibly express Xist in male animals
• Xist expression in males induces autoantibodies and autoimmune pathology
• Xist in males reprograms T and B cell populations to female-like patterns
• Autoantibodies to Xist RNP characterize female-biased autoimmune diseases in patients
Summary
Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long non-coding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation. Here, we show that the Xist ribonucleoprotein (RNP) complex comprising numerous autoantigenic components is an important driver of sex-biased autoimmunity. Inducible transgenic expression of a non-silencing form of Xist in male mice introduced Xist RNP complexes and sufficed to produce autoantibodies. Male SJL/J mice expressing transgenic Xist developed more severe multi-organ pathology in a pristane-induced lupus model than wild-type males. Xist expression in males reprogrammed T and B cell populations and chromatin states to more resemble wild-type females. Human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST RNP. Thus, a sex-specific lncRNA scaffolds ubiquitous RNP components to drive sex-biased immunity."
Graphical abstract
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