PARIS, Oct. 6 (Benin News) –
A new study may have solved the mystery of Crohn’s disease, an inflammatory bowel disease in which immune defenses meant to attack invading microbes mistakenly target the body’s own digestive tract, its authors publish in the magazine “Nature”. Norovirus, a common infection that causes vomiting and diarrhea, is one of many viruses and bacteria thought to trigger the onset of Crohn’s disease in patients with this disease, but the reason is unknown.
The clue came when previous studies found that a certain genetic change (mutation) was present in most patients with the disease. This mutation makes the cells of the intestinal mucosa more vulnerable to damage. However, the mystery thickened once more when it was learned that half of Americans carry this same risky genetic mutation, but less than half a million of them develop Crohn’s disease.
The new work in mice and human tissue reveals for the first time that, in healthy individuals, immune system defenders called T cells secrete a protein called apoptosis inhibitor five (API5), which signals the immune system to stop attacking the cells of the intestinal wall. This protein adds an extra layer of protection once morest immune damage, so even people with the mutation can have a healthy gut. However, the researchers also found that infection with norovirus blocks the secretion of API5 by T cells in mice bred to have a gnawing form of Crohn’s disease, killing the cells of the intestinal wall in the process.
Led by researchers at New York University’s Grossman School of Medicine, United Statesthis work supports the theory that API5 protects most people with the mutation from disease, until a second trigger, such as a norovirus infection, causes some to cross the threshold of the mutation. sickness.
In experiments involving mice genetically engineered to exhibit the mutation linked to Crohn’s disease in humans, mice injected with API5 survived, while half of the untreated group died. This confirmed the idea that the protein protects intestinal cells, say the study authors. In human tissues, the researchers found that people with Crohn’s disease had five to ten times fewer API5-producing T cells in their gut tissues than people without the disease.
“Our results offer new insight into the key role of apoptosis inhibitor five in Crohn’s disease,” says lead study author and gastroenterologist Yu Matsuzawa-Ishimoto. This molecule might constitute a new target for the treatment of this chronic autoimmune disease, which has proven difficult to manage in the long term.
Matsuzawa-Ishimoto, a postdoctoral researcher at NYU Langone Health, points out that current therapies, which work by suppressing the immune system, put patients at high risk of infection and often lose their effectiveness following a few years of use. A targeted therapeutic approach to API5, he adds, might avoid these problems.
In another series of experiments, the researchers created organ-like structures from tissue taken from humans who tested positive for the mutation. In particular, these structures consisted solely of cells from the intestinal mucosa. The research team then introduced API5 into these “mini-guts” and found that this treatment protected the cells in the gut wall. Furthermore, the addition of API5-producing T cells also protected the intestinal mucosa.
“The results of our research help explain why the genetic links to Crohn’s disease are much broader than the actual number of people who have it,” says study co-author and biochemist Shohei Koide, a professor at Department of Biochemistry and Molecular Pharmacology at NYU Langone and a member of its Perlmutter Cancer Center.
“Our study suggests that when norovirus infects people whose ability to produce inhibitor of apoptosis 5 is impaired, it tips the scales towards a full-fledged autoimmune disease,” adds the study co-author and microbiologist Ken Cadwell, Recanati Family Professor of Microbiology at NYU Langone.
Cadwell cautions that although the study authors obtained the API5 protein from human tissue rather than rodents, it is uncertain whether the injectable treatment can be safely administered in humans.
The research team now plans to explore the long-term effects of API5 injections to better understand whether this prospective treatment can effectively control Crohn’s disease, which can present with repeated flare-ups over a long period of time.