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Mon Nov 04 10:54:49 CET 2019

Researchers of the IBGM (Institute of Molecular Biology and Genetics) study through human intestine cells the mechanism which produces Crohn´s disease and ulcerative colitis

In cooperation with several specialists of the Hospital Clinico Universitario and the Hospital Universitario Rio Hortega in the treatment of these diseases which the biologic samples provides for doing the research
With this new model of research, the group led by David Bernardo, researcher of the “Ramon y Cajal”, will try to figure out why the dendritic cells in charge of the immune system defense “are wrong” and order to attack the intestine bacteria

A group of research from the Institute of Molecular Biology and Genetics (IBGM by its abbreviation in Spanish) of the University of Valladolid and of the CSIC (The Spanish National Research Council) of the University of Valladolid has been the first ones in using the dendritic cells of the human intestine in order to discover the mechanism which the intestinal inflammation produces in the Crohn´s Disease and the ulcerative colitis.

For his research, the researcher David Bernardo has created a team in which different specialists collaborate. These specialists work in the diagnosis and the treatment of these diseases, formed by immunologists, gastroenterologists, intestine surgeons and anatomic pathologists from the Hospital Clinico Universitario and the Hospital Universitario Rio Hortega. The project is funded through a 12000 euros fellowship from the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU). Its goal is to develop this project for two years, and it’s the third consecutive time Mr. Bernardo obtained this research fellowship, although it is the first time he obtains it from the University of Valladolid.

Bernardo joined the IBGM in March with a “Ramon y Cajal” program. In the IBGM in 2008, he made his doctoral dissertation about Immunology of celiac diseases, and after that, he specialized in the research of dendritic cells during his stay in the Imperial College London (2009-2015) and the Health Research Institute of the Hospital Universitario de la Princesa in Madrid (2015-2019).

“There I tried to enrich the cells and I started to work with biopsies. After three years without progress, when I joined here I suggested a new work model which allow me to work with patients biopsies and besides tissue obtained from the bowel resections. For this reason, I contacted the digestive system services, the surgery services and the anatomopathological services of both hospitals in Valladolid, so they provided me the required clinical samples (after receiving the ethical relevant approvals) for working”, says the researcher.

Until now, as David Bernardo has done, all the researches were done with material coming from mice and/or cells manipulated in the lab.

The dendritic cells are in charge of ordering the lymphocytes to attack the pathogenic bacteria which can produce disease, without them the immune system does not work. They are a small fraction of the immune system´s cells, and they have crucial importance inside the intestine.

It is precisely because they are a few of them and they die very quickly (they live three days), and this is the reason why we did not plan this research, which most of the researchers focused on the T lymphocytes, which however act under the orders of these dendritic cells.

The dendritic cells are included in the immune system, as well as a judge is within the legal system. This cell determinates everything. Our hypothesis is the inflammatory bowel disease, which includes the Crohn’s Disease and the ulcerative colitis, is provoked by an impaired response of these cells, which produces the disease”-explains David Bernardo.

“All people have benign bacteria in their intestine. Moreover, in patients with Crohn´s disease and ulcerative colitis, the dendritic cells are wrong and they detect the intestinal flora as an enemy to whom they attack. It is known that there are a group of genetics, immunologic, environmental and microbial factors that interact among them complexly and cause the dendritic cells are wrong, but to figure out why these cells are wrong in certain patients is the key question”-adds he.

Until now it is known these cells carry out inflammatory responsiveness against the invading pathogens, while on the contrary, they establish tolerant responsiveness against the gastrointestinal microbiota and the nutrients. To know the mechanisms which activate one path or another will allow that when the pathologic responsiveness activates it could be tried to bring it to the other side.

“For example, for some reason, there is a distribution of the inflammation in Crohn´s Disease and ulcerative colitis which affects some concrete and predetermined areas. In ulcerative colitis, it always affects the rectum and continues towards the colon, but it never arrives at the ileum. The questions we made ourselves are: Why certain areas get frequently inflamed? Why the pre-inflamed cells do not produce inflammation through the entire intestine?  Is there something that protects the tissue and for this reason, it does not inflame it? Or, Is there something predisposed in that part of the intestine which triggers the inflammation?-informs David Bernardo.

The researcher hopes to obtain with this new research model the answers to all the questions in this research of the dendritic cell, “as the way of fighting the “insurrection” of these cells is manipulating the immune system with substances which the own organism produces and which will allow restoring the damaged mechanism due to the Crohn´s disease and the colitis”-concludes he.

Crohn´s Disease

Crohn´s disease is an inflammatory chronic process in the gastrointestinal tract, which affects especially to the lowest small intestine (ileum) and the largest intestine (colon and rectum), although it could cause damage to any part of the digestive tract.

It is unknown the exact reason which causes inflammation. However, all theories suggest an immunologic reason (the body´s defense system) together with an accumulation of certain bacteria.

It could affect people of any age, but most of the patients are young adults between 16 and 40 years old.

Nowadays there are more than 3000 patients in Valladolid diagnosed with ulcerative colitis or Chron´s disease. The medical treatment prices vary between 2000 and 3000 euros per month in some cases and sometimes it could require intestinal surgery with relative frequency.

 

Ramón y Cajal Program
In the foreground Luis Fernández, professor of the UVa and gastroenterologist in Hospital Clinico; David Bernardo, researcher in the IBGM, and Carlota Rivera, Chemistry Student which is doing her senior thesis. In the background, José Antonio Garrote, professor of the UVa and specialists in Clinical Analysis in the Institute of Molecular Biology and Genetics of the Hospital Universitario Rio Hortega
Ramón y Cajal Program
Specialists in the Hospital Clinico Universitario and in the Hospital Rio Hortega of Valladolid collaborate in this research project of the IBGM