They found a weak spot in our DNA that is present in 95% of people with the disease. It makes it much easier for some immune cells to go haywire and drive excessive inflammation in the bowels. The team have found drugs that already exist seem to reverse the disease in laboratory experiments and are now aiming for human trials.
The “weak spot” is an enhancer region about 290 Kbp from the gene ETS2 mentioned elsewhere in the comments. The haplotype associated with IBS leads to overepression of the gene. They did some nice cell and molecular work to confirm the enhancer’s effect on the gene and the genes effect on inflammation response.
It’s the woman in the thumbnail, isn’t it? She’s been causing it?
Five bucks says this will be more useful than for just IBD.
From the abstract: "By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis3,4,5,6—we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. "
I guess you owe me five bucks.
What? I put money that it’d be useful for MORE than IBD. You bring evidence of what I was putting money on.
Ankilosi spondylitis is quite different than IBD.
This is exactly why I’m not a gambler. ;-) I really prefer it when people say things like, “wow, thanks, here have a fiver.”
It was her all along!
A disease-associated gene desert directs macrophage inflammation through ETS2 https://www.nature.com/articles/s41586-024-07501-1
Abstract
Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis3,4,5,6—we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.
I also saw the thumbnail and had a laugh.
“major cause found!” – image of woman’s face
*A major cause of inflammatory bowel disease (IBD) has been discovered by UK scientists.
They found a weak spot in our DNA that is present in 95% of people with the disease.
It makes it much easier for some immune cells to go haywire and drive excessive inflammation in the bowels.*
