Cells that initiate gluten intolerance in people with celiac disease discovered

A rare type of cell digestive system captures proteins from the gluten from inside the intestinetransports them to immune cells and presents them as enemies so that the immune system develops antibodies against them, according to research from the University Hospital of Utrecht (Netherlands) that reveals how gluten intolerance begins in celiac disease.

The researchers presented their results in Nature magazinewarn that the discovery will not improve the lives of people with celiac disease in the short or medium term.

The cells that have been identified as responsible for start celiac disease are the so-called M cells (or microfolded cells) that reside in the wall of the small intestine. Until now they have been assigned a police function.

They monitor what circulates through the intestine and, if they detect suspicious elements such as Bacteriathey stop them. Once arrested, they are taken to the nearest police station. Specifically, they take them to the mucous membranes of the digestive system where they are found. T cells of the immune system who will pass sentence: the criminals must be eliminated.

Celiac disease and findings. Photo: Pexels

Discovery will not improve therapies in the near future, researchers warn

The new research shows that M cells not only capture viruses and bacteria but also they can be wrong and stop innocents like gluten proteins. The most novel discovery is that M cells They not only act as police but also as prosecutors.

They present gluten as the culprit before antibody-producing T cells. These cells, given the evidence that gluten is an antigen, produce antibodies against it. From that moment on, if gluten enters the digestive system again, it will be attacked.

“M cells contribute to the initiation of celiac disease by directly activate CD4 T cells [productoras de anticuerpos] specific for gluten,” he declares in an email to L a Vanguardia. Sangho Limfirst author of the research.

“M cells contribute to the initiation of celiac disease by directly activating CD4 T cells.” [productoras de anticuerpos] specific for gluten” Photo: Pexels

“They could also participate in the long-term progression of the disease by amplifying immune responses”, although Lim warns that the project has focused on the capacity of the cells M to activate the immune system and not in its effects over time.

Regarding the prospects of improving the treatment of celiac disease by acting on M cells, Lim warns that “it would be difficult because M cells do not only capture gluten antigens.”

Since they participate in the immune surveillance of the digestive system, “blocking its functions could have adverse effects«In addition, he adds, once the production of antibodies against gluten has started, the autoimmune reaction can occur even without M cells.

Research for celiac therapies

The current search for therapies for celiac disease is based, on the one hand, on acting on the immune system to mitigate adverse reactions to gluten and, on the other hand, to act on gluten to prevent it from stimulating the immune system. There are ongoing clinical trials of fdrugs against gluten enzyme TG2which makes it immunogenic; against the IL-15 protein of the immune system, which has an important role in celiac disease; or drugs that increase gluten tolerance.

The new research, led by Hans Clevershas been based on organoids. These are tissues created in the laboratory from stem cells that simulate real organs, which allows us to study how biological systems develop and function.

The researchers have compared the active genes in M ​​cells with the results of a previous genomic study of 4,533 people with celiac disease.

The four genes most closely associated with gluten intolerance are activated in M ​​cells. Photo: Pexels

According to results presented December 10 in Nature, the four genes most closely associated with intolerance to gluten are activated in M ​​cells. In addition, M cells have a large amount of IL-15 protein receptorsone of the targets of the drugs that are in development for celiac disease.

Experiments have confirmed that M cells develop from intestinal tissueand not from the bone marrow like the cells of the immune system, something that was already known. But they have revealed that some of the genes that are activated in M ​​cells coincide with those of the dendritic cells of the immune system, which are specialized in capturing enemies and presenting them to T cells. M cells, despite developing like intestinal cells, they behave like immune cellsthe researchers conclude.

Joseph Corbella