Turncoat T Cells Underlie Assault On Small Intestine

The protein found in wheat, barley, and rye can cause severe intestinal symptoms in those who have celiac disease, and researchers at Columbia University in New York have now pinpointed certain immune system cell signatures that underlie the condition.

Turncoat immune system cells associated with celiac disease proliferate in response to dietary gluten, a protein present in some cereals. Consuming gluten increases inflammation, causes bloating, gas, constipation, and even stunts growth in children who are predisposed to the disease. Even if those symptoms are severe, they are only a few of a vast and intricate list.

Currently, researchers at the Columbia Center for Translational Immunology are working to solve the immunological conundrum of celiac disease, a condition for which there is currently no cure and only effective treatment is avoiding gluten. The World Health Organization estimates that one in 100 people worldwide are affected by the illness.

Every organ in the body may be affected by the disorder’s inflammatory consequences, and although sufferers may follow a gluten-free diet, it’s possible that close to 50% still have symptoms despite doing so. Furthermore, despite the fact that eating gluten is a well-known cause of celiac disease, the precise immunological alterations in the intestine involving two subsets of T cells have until now been only vaguely understood.

The team from New York City has revealed many pathways and cell types that underlie celiac disease in a paper published in Science Immunology. This work has enabled them to solve some of the condition’s lingering immunological puzzles. For instance, the researchers found that ingesting gluten causes two important subsets of T cells—alpha-beta and gamma-delta intraepithelial T cells—in the small intestine to undergo a fast reprogramming.

Dr. Adam Kornberg, the study’s primary author, and his colleagues looked at samples of the upper small intestine from 11 individuals with active celiac disease who had not yet started gluten-free diets to better understand the illness’s natural history. In addition, 19 celiac disease patients who had previously abstained from gluten but later consumed it again, as well as 17 healthy subjects, were included in the study. The team’s research identified the distinct cellular fingerprints linked to the diseases.

“Celiac disease is an autoimmune disease in which intestinal inflammation is induced by dietary gluten,” explained Kornberg and a team of colleagues reporting in Science Immunology. “We performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different celiac disease states and healthy controls.

“Untreated, active, and potential celiac disease were associated with an enrichment of activated intestinal T cell populations, including CD4⁺ follicular T helper cells, regulatory T cells, and natural CD8⁺ αβ [alpha-beta] and γδ [gamma-delta] T-intraepithelial cells,” Kornberg added.

In fact, the attack on the small intestine, which explains how bad celiac disease is, involves a broad repertory of T cells. However, gluten directly causes the reprogramming of intraepithelial T cells and natural memory, resulting in a bad inflammatory state in the gut. The scientists discovered that giving participants in the study a gluten challenge—eating gluten as part of the study—caused a reprogramming of the important T cell subsets.

The conventional scientific wisdom has long thought that interactions between helper and intraepithelial T cells, which lurk in the gut and peripheral blood, were the only immune system cells that could account for alterations in the intestine. However, definitive proof of this remained elusive. This notion regarding the processes that underlie celiac disease is corroborated by the latest study, which offers important new evidence.

Other names for the condition include celiac sprue and gluten-sensitive enteropathy. Whatever name it goes by, it harms the small intestine’s lining. It may be important to understand what happens in the gut when gluten is present in order to better comprehend the illness. Gluten is perceived by patients with celiac disease to be an antigen, a foreign invader that not only activates T cells but also causes an inflammatory reaction. People with celiac disease experience flattened, altered tiny intestinal cells that are unable to absorb vitamins and minerals.

Not only are intestinal cells remodelled, but their paralyzed state also opens the door to a host of health issues. Chronic illnesses that develop as a direct result of a persistent inflammatory response and nutritional deficits can range from anemia and obvious skin rashes on the elbows, knees, torso, and scalp. Upon diagnosis, it is typical to discover deficiencies in fiber, iron, calcium, magnesium, zinc, folate, niacin, riboflavin, vitamin B12, and vitamin D in celiac disease patients.

According to the Celiac Disease Foundation in Woodland Hills, California, there is a one in ten risk that an individual may also get celiac disease if they have first-degree relatives who have the condition. Furthermore, while prompt diagnosis is essential for treating the ailment, it might take patients six to ten years to acquire a precise diagnosis. According to doctors at the foundation, type 1 diabetes, intestinal cancer, osteoporosis, thyroid disease, multiple sclerosis, infertility, and miscarriage can all result from celiac disease if it is not diagnosed in a timely manner.

Additionally, they point out that celiac disease affects more children than cystic fibrosis, Crohn’s disease, and ulcerative colitis combined. However, microscopic colitis and inflammatory bowel illness are more common in those with celiac disease. Furthermore, multiple studies have indicated that the likelihood of acquiring another autoimmune ailment increases with the age at which celiac disease is first diagnosed.

The Columbia Center for Translational Immunology team hypothesizes that the fresh insight they have provided into the function of the T cell repertoire in celiac disease may help throw light on related pathways underlying other autoimmune illnesses.  “Because [celiac disease] shares traits with other autoimmune diseases, these findings should prove informative beyond celiac disease,” Kornberg and the other authors concluded.

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