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Key proteins that link genetics to environmental influences
Update time:2019-10-08 00:51:33   【 Font: Large  Medium Small

Researchers at Harvard medical school have identified a protein called epigenetic regulator that is mutated in many autoimmune diseases: SP140, which is also essential for macrophage function and intestinal homeostasis. "Many immune-mediated diseases are driven by a combination of genetic predisposition and environmental influences, and epigenetics is a key link between the two," says Kate Jeffrey, a researcher in innate epigenetic regulation at Harvard medical school.
The researchers used chip-SEQ to isolate the epigenetic reader and bind the DNA on it, and found that SP140 occupied the transcription initiation site in human macrophages. If you remove SP140 from macrophages (from mice) in the cell culture, the ability of macrophages to be activated is severely impaired. In addition, when the team knocked out the SP140 gene in the model mice's immune system, they found that the absence of this epigenetic regulator weakened the rodents' gut defense barrier, altered the balance of their gut microbes and increased intestinal inflammation.
"SP140 can change the body's response to pathogens and can make colitis worse," Jeffrey said. But we don't know what happens when SP140 becomes infected in the body.
"Initially, when we found that this epigenetic mediated factor was immunologically limited, we thought it might be an important therapeutic target because there would be no missed targets," Jeffrey said. But it turns out that if you don't have it, it causes inflammation in the gut, so you can't inhibit it."

"This is a very comprehensive study that describes a previously unknown molecular mechanism of the innate immune system," said Xinnan Wang, professor of immunology at Stanford University School of Medicine.

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