Mutations in a gene linked to Crohn’s disease strip vital immune cells of their ability to switch modes, leading to an exaggerated response and inflammation, a recent study found, according to ScienceAlert. Although previous research has linked variations in the NOD2 gene to Crohn’s disease, its exact function in the pathophysiology of the condition has long been unknown.
Scientists use AI to understand macrophages and gut
Researchers at the University of California, San Diego used machine learning techniques to find trends in the gene activity of immune cells in the gut.
The mutations disrupt the normal protective mechanisms that allow NOD2 proteins to prevent IBD, according to experiments done on lab-grown cells and samples from healthy stomachs and digestive tracts with a type of Crohn’s disease known as inflammatory bowel disease (IBD).
By monitoring the gene expression of immune cells known as macrophages, the researchers were able to identify which cells maintained gut health and which developed inflammation and caused damage.
“The gut is the battlefield, and macrophages are the peacekeepers,” said UC San Diego’s Gajanan Katkar. “For the first time, artificial intelligence has allowed us to clearly define and track players in two opposing teams,” he added.
In the stomach, macrophages can alternate between two states: an inflammatory state to fight infection and a non-inflammatory state to repair damage. It is known that a healthy stomach depends on maintaining a balance between these two conditions.
The 53 genes that made up the genetic profile of the study team regulated macrophage status in IBD.
Gridin keeps macrophages alert
Girdin is a protein that is produced by a gene that has been shown to promote a non-inflammatory state in macrophages. NOD2 and girdin proteins have been shown to work together to keep macrophages alert to danger without becoming unduly reactive. Without them, macrophages in attack mode are excessively inflammatory and macrophages in repair mode are less efficient at clearing targets.
“NOD2 functions as an infection surveillance system in the body,” says Pradipta Ghosh, a cell scientist at UC San Diego. “When bound to girdin, it detects invading pathogens and maintains the immune balance of the gut by rapidly neutralizing them. Without this partnership, the NOD2 surveillance system breaks down,” explained Ghosh.
According to the researchers, these findings shed “new light on the molecular pathways underlying intestinal homeostasis and IBD progression.”
Frequently asked questions
1. What is Crohn’s disease?
Crohn’s disease is a long-term condition that causes swelling in parts of the digestive system. It can lead to stomach pain, diarrhea, weight loss and fatigue.
2. How is Crohn’s disease treated?
There is no cure, but treatment helps control symptoms. Doctors may use medications to reduce inflammation, dietary changes, and sometimes surgery if symptoms worsen.
