Tuesday, 02 January 2024 12:17 GMT

What Are Macrophages? Study Reveals Crucial Genetic Mutation Behind Crohn's Disease


(MENAFN- Live Mint) Mutations in a gene linked to Crohn's disease deprive vital immune cells of their capacity to change modes, which leads to overreaction and inflammation, a recent study has found, per ScienceAlert. Although prior research connected variations in the NOD2 gene to Crohn's disease, its precise function in the pathophysiology of the condition had long been unknown.

Researchers use AI to understand macrophages and the gut

Researchers from the University of California, San Diego, employed machine learning techniques to find trends in the gene activity of immune cells in the gut.

The mutations disrupt normal protective mechanisms that enable NOD2 proteins to prevent IBD, according to experiments conducted on lab-grown cells and samples from both healthy stomachs and digestive tracts with a kind of Crohn's illness known as inflammatory bowel disease (IBD).

By monitoring the expression of the genes of immune cells known as macrophages, the researchers were able to identify which cells maintained gut health and which developed inflammation and caused harm.

"The gut is a battlefield, and macrophages are the peacekeepers," UC San Diego Gajanan Katkar said. "For the first time, AI has allowed us to clearly define and track the players on two opposing teams,” he added.

In the stomach, macrophages can alternate between two states: an inflammatory state for fighting infection and a non-inflammatory state for repairing damage. A healthy stomach is known to depend on maintaining a balance between these two states.

The 53 genes that made up the study team's genetic profile regulated the macrophage status in IBD.

Gridin keeps macrophages vigilant

Girdin is a protein that is produced by a gene that has been shown to support the non-inflammatory macrophage state. It turns out that NOD2 and girdin proteins cooperate to keep macrophages vigilant about dangers without becoming unduly reactive. Without them, attack-mode macrophages are excessively inflammatory, and repair-mode macrophages are less effective in cleaning up targets.

"NOD2 functions as the body's infection surveillance system," says Pradipta Ghosh, a cell scientist at UC San Diego. "When bound to girdin, it detects invading pathogens and maintains gut immune balance by swiftly neutralising them. Without this partnership, the NOD2 surveillance system collapses,” Ghosh explained.

According to the researchers, the insights shed“new light on the molecular pathways underlying gut homeostasis and the progression of IBD”.

FAQs1. 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 tiredness.

2. How is Crohn's disease treated?

There is no cure, but treatment helps control symptoms. Doctors may use medicines to reduce inflammation, changes in diet, and sometimes surgery if symptoms get worse.

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