Clue to Link Between Mutations in Autophagy Genes and Crohn’s Disease; Alternative Pathogen-Fighting System Uses Some of Autophagy’s Cellular Machinery

Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn’s disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers at the University of Texas (UT) Southwestern Medical Center have uncovered an intriguing clue. A research team led by Dr. Lora Hooper, Chair of Immunology at UT Southwestern and an Investigator of the Howard Hughes Medical Institute, has determined that a backup pathogen-fighting system uses autophagy’s cellular machinery to deliver protein weapons to the front lines – the cell surface – in the fight against bacterial attack. “This is the first example of this alternative pathway being used in immune defense in any kind of animal,” Dr. Hooper said of the mouse study, published online today (Juley 27, 2017) in Science. The article is titled “Paneth Cells Secrete Lysozyme Via Secretory Autophagy During Bacterial Infection of the Intestine.” The Centers for Disease Control and Prevention (CDC) estimates that approximately 3 million U.S. residents suffer from inflammatory bowel disease with that number about equally split between Crohn’s disease and ulcerative colitis. The two conditions are characterized by chronic inflammation of the gastrointestinal tract. Dr. Shai Bel, a postdoctoral researcher in Dr. Hooper’s laboratory and the lead author of the study, said the significance of the study’s findings rests on understanding the complex, dynamic ecosystem in the intestines. “Our guts are teeming with trillions of bacteria that do a great service by helping us digest food, but they can also cause illness if able to invade our tissues,” Dr. Bel said.
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