Hormone receptor a potential target in Crohn's therapy

crohn's
Granulomas with giant cells in an intestinal lymph node in a patient with Crohn's disease

University of British Columbia scientists have found a genetic mutation that protected mice from scarring of intestinal tissue similar to that caused by Crohn’s disease. In addition to potential applications in Crohn’s therapy, the team hopes the findings can also inform treatments for other inflammatory diseases.

Crohn’s is a chronic inflammatory bowel disease that can cause fibrosis--the thickening and scarring of tissue--in some patients’ intestines and cause obstruction. The team discovered a group of cells that drive fibrosis in a mouse model of Crohn’s: RORα (RAR-related orphan receptor alpha) and group 3 innate lymphoid cells, according to a statement.

Mice in which RORα was switched off did not develop fibrosis after being infected by a type of salmonella that causes Crohn’s-like symptoms, the scientists said. The findings are published in Science Immunology.

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"We found what we think are the inflammatory cells that drive fibrosis," said co-author Kelly McNagny, professor of medical genetics and co-director of the UBC Biomedical Research Centre, in the statement. "The gene that was defective in those cells is a hormone receptor, and there are drugs available that may be able to block that hormone receptor in normal cells and prevent fibrotic disease."

There is currently no cure for Crohn's disease. Many patients who develop intestinal fibrosis must undergo surgery to restore digestion, but scar tissue can build up following surgery, necessitating more procedures in the future.

While their focus was Crohn’s disease, the research has implications for other inflammatory diseases: "Fibrosis is a response to chronic inflammation, but it is also a process that occurs during normal aging. If you can reverse this, you've essentially found a way to promote regeneration rather than degeneration," said lead author Bernard Lo, a Ph.D. candidate at UBC, in the statement.

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