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A study on celiac disease looks at how damage is caused by gluten specifically.

When one has celiac disease, eating a bagel involves chewing and savoring, the flavor of the high-gluten bread being made even more delectable by the knowledge that one will go to hell for doing so.

The bagel is then broken down and divided into digestible and non-digestible components; gliadin, a protein contained in gluten, remains in the intestines.

Then things start to go wrong from there. When immune cells encounter gliadin, they panic out and unleash a severe inflammatory reaction that causes pain and intestinal damage.

It is unknown exactly how that damage occurred and why it affects only approximately 1% of the population when so many more people have a higher genetic risk of developing celiac disease or have a milder immune response.

However, new research that was just published on Friday in Science Immunology suggests a mechanism that may be at work in other autoimmune diseases and offers a potential explanation for how intestinal lesions caused by T cell outbursts are caused.

Celiac disease is an autoimmune disorder of the small intestine that can result in a wide range of symptoms, including poor nutrient absorption, recurrent diarrhea and exhaustion, mental fog, osteoporosis, and more.

Gastroenterologist Arnold Han, the paper’s senior author, has been researching celiac disease for more than ten years. He also observed the researchers’ discovery that intestinal damage was not solely caused by CD4+ T cells. Instead, the field started to notice that the GI tract was being affected by a population of T cells called T-IELs.

Even though some of these T-IELs don’t identify and kill gluten the same manner as other T cells do, they were activating in celiac patients. Natural killer receptors on the T-IELs notify them to a problem that needs to be resolved, like as a virus or tumor.

The majority of celiac disease models have hypothesized that the initial conflict between the tantrum-throwing CD4+ T cells and gliadin was causing inflammation, which in turn triggered the T-IELs to damage the intestinal mucosa. But the newest research suggests a different viewpoint.

Han, an assistant professor in the departments of medicine and microbiology and immunology at Columbia University, stated, “One thing that we observed, somewhat surprise, is that these NK receptor-expressing IELs are truly triggered very, very swiftly and intentionally by gluten.

The study, according to Ludvig Sollid, a well-known celiac researcher at Oslo University Hospital in Norway, provided a thorough characterization of the various T cells involved in the illness. He also highlighted the question of whether CD4+ T regulatory cells in celiac disease still play a role in the pathogenesis of the illness.

He found the paper’s conclusion regarding the harmful combination of T-IELs and natural killer receptors to be the most intriguing.

Han is accustomed to some controversy. Han made the claim that several types of T cells were activated simultaneously when a person with celiac consumed gluten while working as a postdoc in the Stanford lab of another celiac researcher, Mark Davis. His findings revealed the presence of CD4+ cells in the blood alongside tumor-scanning CD8+ T cells and distinctive gamma delta T cells.

That idea, however, “was kind of discounted by the field,” he claimed, and the T cells were written off as regular, recirculating presences that were unrelated to a systemic inflammatory response brought on by gluten.

His most recent article strengthens the argument that gluten activates multiple types of T cells at once and that these cells are not just present due to recirculation.

According to the data, which were derived from small intestine biopsies taken from 37 patients with various stages of disease and 17 healthy volunteers, T-IEL cells change from being anti-inflammatory to pro-inflammatory before killing intestinal tissue. That aspect was actually somewhat unexpected, Han added.

He claims that there has been a friendly thumb war between celiac researchers for many years. Do T cells activate simultaneously? How significant is the CD4+ response? Each person builds on the work of the others and examines novel hypotheses. Some experts in the field have recently believed that CD4+ cells’ disease-causing immune response is suppressed by tumor-fighting CD8+ T cells.

Han’s evidence, however, clearly refutes that claim and instead suggests that CD8+ cells are a destructive force. He claimed that it “sort of goes against these other, very provocative models that are being proposed.” “The field should decide how to handle this. We further emphasize that the models do not conflict with one another.

It is important to understand the mechanism by which gluten affects the immune system and causes the type of intestinal damage that has a negative influence on certain people’s life since it may lead to a cure. “We know that these bad, probably tissue-damaging populations, they’re present in patients with potential celiac disease who don’t have damage,” said first author Andrew Kornberg, a Ph.D. candidate. “We have some theories about why they aren’t harming the tissue there.

However, those would make excellent targets for a therapy to keep these people in check for the rest of their lives and prevent them from developing into patients who have actual tissue damage.

Furthermore, since gluten is a known and manageable trigger of celiac disease, understanding how T cell-driven autoimmunity functions in this condition may offer helpful insights into how other autoimmune diseases develop, according to Han.

There are several open-ended questions that need to be answered, such as how exactly CD4+ activates all of these immune cells. What function do these T cells serve in regular biology? How do they end up being used to destroy healthy tissue? Given the high prevalence of possible celiac disease without gut lesions, Kornberg surmises that the T-IELs require a “last little boost” to cause intestinal tissue destruction. But more investigation will be required to determine what precisely that last push is.

Bloomberg Philanthropies has provided funding to STAT to support its coverage of chronic health problems.

No decisions regarding our journalism are made with the participation of our financial backers.



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