Celiac.com Sponsor (A1):



Celiac.com Sponsor (A1):


  • Join Our Community!

    Get help in our celiac / gluten-free forum.

  • Jefferson Adams

    Have Researchers Found the Destructive Key Behind Celiac Disease?

    Jefferson Adams
    2 2
    Reviewed and edited by a celiac disease expert.   eNewsletter: Get our eNewsletter

      Do interleukin-15 gluten and HLA-DQ8 drive tissue destruction in celiac disease?


    Caption: Image: CC BY 2.0--National Eye Institute

    Celiac.com 02/17/2020 - Celiac disease is a common inflammatory autoimmune disorder triggered when dietary gluten causes intestinal damage in genetically susceptible people who have either of two genes, the HLA-DQ8 or HLA-DQ2 haplotypes. 

    More and more, doctors see a need to come up with non-dietary treatments, but there is currently no good gluten- and HLA-dependent model. Human data has led to a great deal of information about the origins of celiac disease, but no one has yet revealed the roles of disease-predisposing HLA molecules, and of adaptive and innate immunity in celiac-related tissue damage. 



    Celiac.com Sponsor (A12):




    A large team of top researchers recently set out to determine if interleukin-15 gluten and HLA-DQ8 drive tissue destruction in celiac disease.

    The research team included Valérie Abadie, Sangman M. Kim, Thomas Lejeune, Brad A. Palanski, Jordan D. Ernest, Olivier Tastet, Jordan Voisine, Valentina Discepolo, Eric V. Marietta, Mohamed B. F. Hawash, Cezary Ciszewski, Romain Bouziat, Kaushik Panigrahi, Irina Horwath, Matthew A. Zurenski, Ian Lawrence, Anne Dumaine, Vania Yotova, Jean-Christophe Grenier, Joseph A. Murray, Chaitan Khosla, Luis B. Barreiro and Bana Jabri.

    The team used a mouse model to mimic the over-expression of interleukin-15 (IL-15) in the gut epithelium and lamina propria that marks active celiac disease, carries HLA-DQ8, and shows villous atrophy after gluten exposure.  

    For villous atrophy to occur, IL-15 must be over-expressed in both the epithelium and the lamina propria, which shows the crucial role of IL-15 in the development of celiac disease. 

    Moreover, CD4+ T cells and HLA-DQ8 play a central part in permitting cytotoxic T cells to mediate intestinal epithelial cell lysis. 

    The team's results also demonstrate a role for the cytokine interferon-γ (IFNγ) and the enzyme transglutaminase 2 (TG2) in tissue destruction. 

    By revealing the intricate interplay between gluten, genetics and IL-15-driven tissue inflammation, this mouse model casts light on the mechanisms behind celiac disease, and may help to drive the development of new treatments.

    Read more at Nature.com

     

    The researchers are variously affiliated with the Department of Medicine, University of Chicago, Chicago, IL, USA, Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA; Committee on Immunology, University of Chicago, Chicago, IL, USA; the Department of Biology, University of San Francisco, San Francisco, CA, USA; the Department of Chemistry, Stanford University, Stanford, CA, USA; the Department of Chemical Engineering, Stanford University, Stanford, CA, USA; the Stanford ChEM-H, Stanford University, Stanford, CA, USA; the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; the Department of Immunology, Mayo Clinic, Rochester, MN, USA; the Department of Dermatology, Mayo Clinic, Rochester, MN, USA; the Department of Microbiology, Infectiology, and Immunology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; the Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada; Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada; the Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.

    2 2

    User Feedback

    Recommended Comments



    Join the conversation

    You are posting as a guest. If you have an account, sign in now to post with your account.
    Note: Your post will require moderator approval before it will be visible.

    Guest
    Add a comment...

    ×   Pasted as rich text.   Paste as plain text instead

      Only 75 emoji are allowed.

    ×   Your link has been automatically embedded.   Display as a link instead

    ×   Your previous content has been restored.   Clear editor

    ×   You cannot paste images directly. Upload or insert images from URL.


  • About Me

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,500 articles on celiac disease. His coursework includes studies in science, scientific methodology, biology, anatomy, medicine, logic, and advanced research. He previously served as SF Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.


  • Celiac.com Sponsor (A17):
    Celiac.com Sponsor (A17):





    Celiac.com Sponsors (A17):




  • Related Articles

    Jefferson Adams
    Celiac.com 08/06/2009 - A study by a team of Spanish researchers puts the world on notice that gluten may trigger adverse reactions in both celiacs and non-celiacs alike. The research team was made up of E. Arranz, D. Bernardo, L. Fernandez-Salazar, J. A. Garrote and their colleague S. Riestra, all doctors based in Spain.
    According to the current medical wisdom, innate immunity...

    Jefferson Adams
    Celiac.com 03/18/2011 - By blocking an inflammatory protein called interleukin-15 (IL-15), doctors may be able to treat and prevent symptoms of celiac disease in some people, according to a new study in the journal Nature.
    The data suggest that the inflammatory response to gluten in people with celiac disease may be triggered by interleukin-15 and retinoic acid, which is a derivative...

    Jefferson Adams
    Celiac.com 12/22/2016 - The nature of gut intraepithelial lymphocytes (IELs) lacking antigen receptors remains controversial. A team of researchers recently set out to better understand the mechanisms by which innate intraepithelial lymphocytes develop in the intestine and become cancerous in celiac disease patients.
    The research team included J Ettersperger, N Montcuquet, G...

    Jefferson Adams
    Celiac.com 02/15/2020 - Recently, involvement of interleukins IL-19, IL-20 and IL-24 has been reported in inflammatory diseases associated with tissue remodeling. However, researchers know very little about the exact way in which they influence the development and mechanics of celiac disease.
    To get a better understanding of the situation, a team of researchers recently s...