New insights into the mechanisms behind Crohn’s disease point to potential therapeutic target

Aug. 29, 2022
Study results suggest that certain anti-cancer drugs may also target a key player in Crohn’s disease.

The structure of chromatin—the mixture of DNA and proteins that form chromosomes—can affect gene expression, and certain chromatin “readers” are important for monitoring this structure often in response to environmental cues. 

Mutations within one such reader, called Speckled Protein 140 (SP140), are associated with an increased risk of certain immune diseases, including Crohn’s disease, a type of inflammatory bowel disease. 

New research led by investigators at Massachusetts General Hospital (MGH) and published in Cell provides insights into the mechanisms behind this link, pointing to potential therapeutic targets. 

SP140 expression is uniquely restricted to immune cells such as macrophages, which surround and kill microorganisms, remove dead cells, and stimulate the action of other immune cells. 

Protein analyses by Kate L. Jeffrey, PhD, a principal investigator of immunology at MGH and an associate professor of medicine at Harvard Medical School, and her colleagues revealed that SP140 represses topoisomerases (TOP), which are enzymes that help DNA untangle during replication. 

Mass General release