"When they have less Atg16L1, the Paneth cells survive, but their ability to secrete granules is significantly impaired," Cadwell says.
Virgin consulted with co-authors Ellen Li, M.D., Ph.D., and Thaddeus Stappenbeck, M.D., Ph.D., Washington University researchers who study and treat Crohn's disease patients at Barnes-Jewish Hospital. When surgery becomes necessary to repair a patient's bowel, Li collects samples removed from the intestine for research. Selecting tissue from patients with mutated Atg16L1, researchers compared human Paneth cells to cells from their mouse model and found what Virgin calls "striking similarities."
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 an important process called autophagy that lets cells consume and reuse their own resources and may have other functions as well. 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.
"We don't yet know why having abnormal Paneth cells would predispose a person to Crohn's disease or to what degree other genes linked to Crohn's may affect the Paneth cell, but those are just a few of the very interesting questions to follow up on from these results," Virgin says.
|Contact: Michael C. Purdy|
Washington University School of Medicine