A mutation previously associated with the disease decreased Paneth cells’ ability to protect against infection, according to Nature paper.
Researchers have discovered a link between an increased risk of developing Crohn’s disease and damaged Paneth cells, immune cells that line a portion of the small intestine. The team found that the health of these cells is related to a gene previously associated with Crohn’s.
Prior research revealed that a mutation in the Atg19L1 gene increases the risk of Crohn’s. The research team thus created two lines of mice with a genetic alteration that reduced their ability to make the Atg16L1 protein.
The scientists found that decreased Atg16L1 protein affected Paneth cells. These cells package proteins and antimicrobial peptides as granules that can be secreted into the intestines to defend the body against infection.
“When they have less Atg16L1, the Paneth cells survive, but their ability to secrete granules is significantly impaired,” says Ken Cadwell, Ph.D.
Additionally, tissue from Crohn’s disease patients with mutated Atg16L1 showed many similarities to the mouse models used in this study, according to the investigators. Cells in the mouse model had altered genetic activity that could lead to increased production of certain hormones that are elevated in some Crohn’s patients.
To learn how Atg16L1 helps the Paneth cell, scientists conducted a follow-up experiment where a related gene, Atg5, was knocked out in mice. Like Atg16L1, Atg5 contributes to autophagy. Paneth cells in this line of mice had impairments similar to the first line, suggesting that Atg16L1’s contributions to the Paneth cell may be linked to autophagy.
The article appears online this week in Nature. The research was conducted by scientists at Washington University School of Medicine, Barnes-Jewish, and St. Louis Children’s hospitals.