idw – Informationsdienst Wissenschaft

Nachrichten, Termine, Experten

Grafik: idw-Logo
Science Video Project
idw-Abo

idw-News App:

AppStore

Google Play Store



Instance:
Share on: 
11/30/2018 14:07

Towards a treatment for gluten intolerance

Dr. Tilmann Kiessling EMBO Communications
EMBO - excellence in life sciences

    Heidelberg, 30 November 2018 - Celiac disease is a severe autoimmune disorder of the intestine. It occurs when people develop sensitivity to gluten, a substance found in wheat, rye, and barley. An international research team from Italy and France has now uncovered a new molecular player in the development of gluten intolerance. Their discovery, published in The EMBO Journal, suggests potential targets for the development of therapeutic approaches for the disease.

    Heidelberg, 30 November 2018 - Celiac disease is a severe autoimmune disorder of the intestine. It occurs when people develop sensitivity to gluten, a substance found in wheat, rye, and barley. An international research team from Italy and France has now uncovered a new molecular player in the development of gluten intolerance. Their discovery, published in The EMBO Journal, suggests potential targets for the development of therapeutic approaches for the disease.

    Celiac disease can appear in people who are genetically predisposed, but it is triggered through environmental factors. When people suffering from celiac disease eat gluten, their immune system triggers a response against their body’s own cells, damaging the mucosal surface of the small intestine. About 1 in 100 people suffer from celiac disease, but the prevalence is about three times higher in patients who also suffer from cystic fibrosis. “This co-occurrence made us wonder if there is a connection between the two diseases at the molecular level,” said Luigi Maiuri of the University of Piemonte Orientale in Novara and San Raffaele Scientific Institute in Milan, Italy, who led the research together with Valeria Raia (University Federico II of Naples, Italy) and Guido Kroemer (University of Paris Descartes, France).

    Cystic fibrosis is characterized by the build-up of thick and sticky mucus in the patients’ lungs and intestine. It is caused by mutations of the gene coding for cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an ion transport protein that plays an important role in keeping mucus fluid – when it fails, the mucus clogs up. Moreover, CFTR malfunction triggers a number of additional reactions in the lungs and other organs including intestine by activation of the immune system. These effects are very similar to the responses triggered by gluten in celiac patients. Maiuri, Kroemer and their colleagues took a closer look at the molecular underpinnings of these similarities.

    Gluten is difficult to digest, so that relatively long protein parts – peptides – enter the intestine. Using human intestinal cell lines that are sensitive to gluten, the researchers found that one specific peptide, P31-43, directly binds to CFTR and impairs its function. This interaction triggers cellular stress and inflammation, suggesting that CFTR plays a central role in mediating gluten sensitivity in celiac patients.

    Moreover, the interaction between P31-43 and CFTR can be inhibited by a potentiator of CFTR, called VX-770. When intestinal cells or tissue samples collected from celiac disease patients were pre-incubated with VX-770 before being exposed to P31-43, the peptide did not elicit an immune reaction. Thus, VX-770 protects gluten-sensitive epithelial cells from the detrimental effect of gluten. In addition, the researchers found that VX-770 could protect gluten-sensitive mice from gluten-induced intestinal symptoms.

    There is, as yet, no cure for celiac disease; the only therapeutic strategy is to keep a strict diet. However, the current study is a promising step towards the development of a treatment. It suggests that CFTR potentiators, which have been developed to treat cystic fibrosis, may also be explored as a starting point for the development of a remedy for celiac disease.

    A pathogenic role for cystic fibrosis transmembrane conductance regulator in celiac disease
    Valeria R. Villella, Andrea Venerando, Giorgio Cozza, Speranza Esposito, Eleonora Ferrari, Romina Monzani, Mara C. Spinella, Vasilis Oikonomou, Giorgia Renga, Antonella Tosco, Federica Rossin, Stefano Guido, Marco Silano, Enrico Garaci, Yu-Kai Chao, Christian Grimm, Alessandro Luciani, Luigina Romani, Mauro Piacentini, Valeria Raia, Guido Kroemer & Luigi Maiuri


    Original publication:

    Read the article: emboj.embopress.org/cgi/doi/10.15252/embj.2018100101
    doi: 10.15252/embj.2018100101


    Images

    Criteria of this press release:
    Journalists
    Biology
    transregional, national
    Miscellaneous scientific news/publications
    English


     

    Help

    Search / advanced search of the idw archives
    Combination of search terms

    You can combine search terms with and, or and/or not, e.g. Philo not logy.

    Brackets

    You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).

    Phrases

    Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.

    Selection criteria

    You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).

    If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).