Celiac.com Sponsor (A1):


Join eNewsletter


Celiac.com Sponsor (A1-m):



Join eNewsletter
  • Join Our Community!

    Ask us a question in our celiac / gluten-free forum.

  • Jefferson Adams

    Could the Dual Activation of IRF1 and IRF1-Regulated Genes Be a Key to Celiac Disease Symptoms?

    Jefferson Adams
    0
    Reviewed and edited by a celiac disease expert.

      A new study shows that activation of IRF1 and IRF1-regulated genes together, both directly and via the interleukin-18 dependent inflammasome, would greatly increase the severity of the inflammatory response.


    Genes acting in concert could worsen celiac disease symptoms. Photo: CC--Glen Bowman
    Caption: Genes acting in concert could worsen celiac disease symptoms. Photo: CC--Glen Bowman

    Celiac.com 10/18/2017 - Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten.

    A team of researchers recently set out to clarify the role of small intestinal epithelial cells in the immunopathology of celiac disease, especially the influence of celiac disease-associated bacteria.



    Celiac.com Sponsor (A12):






    Celiac.com Sponsor (A12-m):




    The research team included G Pietz, R De, M Hedberg, V Sjöberg, O Sandström, O Hernell, S Hammarström, and ML Hammarström. They are variously affiliated with the Department of Clinical Microbiology, Immunology, and the Department of Clinical Sciences and Pediatrics at Umeå University, in Umeå, Sweden.

    The team collected duodenal biopsies from children with active celiac disease, treated celiac disease, and a group of clinical control subjects.

    They then purified intestinal epithelial cells, and analyzed them for gene expression changes at the mRNA and protein levels.

    To assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells, they used two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers.

    In patients with active celiac disease, intestinal epithelial cells significantly upregulated more than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1.

    Of these genes, 70 percent were upregulated by interferon-γ via the IRF1 pathway. Notably, IRF1 was also upregulated by bacteria associated with celiac disease.

    Intestinal epithelial cells also expressed the NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes.

    Over-expression of IRF1 appears to be a key factor in the epithelial reaction in celiac disease. This may be inherent, but may also be due to presence of undesirable microbes that trigger or influence IRF1.

    From this study, the researchers conclude that activation of IRF1 and IRF1-regulated genes together, both directly and via the interleukin-18 dependent inflammasome, would greatly increase the severity of the inflammatory response, and trigger the pathological gut response that is common in active celiac disease. Could this provide a key to unlocking the mysteries of celiac disease and its associated symptoms?

    Source:

    0

    User Feedback

    Recommended Comments

    There are no comments to display.



    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.   Restore formatting

      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-m):