It’s estimated that over half a million Americans suffer from Crohn’s disease. According to the Mayo Clinic, Crohn’s is a type of inflammatory bowel disease in which immune defenses meant to attack invading pathogens mistakenly target the body’s own digestive tract. However, new research published in the journal Nature found that a protein secreted by our immune defenders, called T cells, signals the immune system to stop the attack on gut lining cells.
The protein is called apoptosis inhibitor 5 (API5), says SciTechDaily, and it adds another layer of protection against damage by the immune system. It’s even effective in individuals who have a genetic mutation that makes them more vulnerable to Crohn’s.
However, the scientists discovered that the very contagious norovirus blocks T cell production of API5 in mice bred to have a rodent form of Crohn’s disease, killing gut lining cells in the process. The team of researchers from NYU Grossman School of Medicine found that API5 protects most people with the mutation against the disease until another trigger, such as a norovirus infection, pushes the disease over the threshold.
In human tissue, the scientists found that people with Crohn’s disease had between 5-and10-fold fewer API5 producing T cells in their gut tissue than those without the condition.
In experiments centered on mice genetically modified to have the mutation linked to Crohn’s disease in humans, mice that received an injection of API5 survived, while half the untreated mice died, according to NYU Langone Health.
“Our findings offer new insight into the key role that apoptosis inhibitor 5 plays in Crohn’s disease,” said gastroenterologist Dr. Yu Matsuzawa-Ishimoto, the study’s lead author. “This molecule may provide a new target for treating this chronic autoimmune illness, which has proven difficult to manage over the long term.”
Current treatments for Crohn’s include therapies that suppress the immune system, which put patients at high risk for infection. A treatment method targeting API5 might avert these issues, says SciTechDaily. The scientists also created “mini guts” out of gut-lining cells collected from individuals with the mutation that makes them more prone to Crohn’s. They dropped API5 into these mini guts and found that the treatment protected the cells and helped produce more T cells that also protected gut lining.
“Our study suggests that when norovirus infects those with a weakened ability to produce apoptosis inhibitor 5, it tips the balance toward full-blown autoimmune disease,” said Ken H. Caldwell, one of the study’s senior authors and a microbiologist at NYU Langone. Caldwell says that we don’t know if the API5 injections can be safely administered in humans, but their research team plans to examine this next step in humans with the hope that it helps people with Crohn’s disease manage the disease effectively.
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