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    Scott Adams

    Understanding Celiac Disease Through Organoid Models: The Role of IL-7

    Reviewed and edited by a celiac disease expert.

    The use of organoids provides a powerful new tool for understanding celiac disease at a cellular level.

    Understanding Celiac Disease Through Organoid Models: The Role of IL-7 - just a copy of... (cc) by marfis75 is licensed under CC BY 2.0.
    Caption:

    Celiac.com 08/21/2024 - Celiac disease is an autoimmune disorder where the ingestion of gluten, a protein found in wheat, barley, and rye, leads to damage in the small intestine. The condition is marked by an immune response that targets and destroys the mucosal lining of the small intestine, causing symptoms such as bloating, diarrhea, constipation, nausea, and gas. The only effective treatment currently available is a lifelong adherence to a strict gluten-free diet. Traditional methods for studying celiac disease include the use of biopsied intestinal tissue, which has limitations in longevity and complexity, or animal models that do not fully replicate the human condition.

    Creation of Celiac Disease Organoids

    Researchers at Stanford Medicine developed a novel approach using organoids to model celiac disease. Organoids are three-dimensional cell cultures that mimic the structure and function of real organs. In this study, organoids were created from the intestinal tissue of individuals with celiac disease. These organoids include multiple cell types, such as epithelial cells, immune cells, and cells from the lining of the gut. This diversity allows the organoids to faithfully reproduce the interactions between different cell types seen in celiac disease patients.

    The Role of IL-7 in Celiac Disease

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    The study revealed that interleukin-7 (IL-7), a molecule previously implicated in autoimmune diseases like rheumatoid arthritis and multiple sclerosis, plays a significant role in celiac disease. When gluten was introduced to the organoids derived from celiac patients, the researchers observed an increase in IL-7 levels, which was associated with immune activation and epithelial cell destruction. Blocking IL-7 activity prevented this damage, suggesting that IL-7 is a critical mediator of the immune response to gluten in celiac disease.

    Findings and Implications

    The researchers found that organoids from celiac patients, when exposed to gluten, showed an increase in IL-15 and the proliferation of CD4 T cells, which recognize gluten, and B cells, which produce antibodies to type 2 transglutaminase (TG2). This cascade of immune responses led to the activation of CD8 T cells that attack and kill epithelial cells. Blocking IL-7 activity in these organoids halted the epithelial destruction, indicating that IL-7 is a crucial factor in the disease mechanism. Furthermore, the study showed that IL-7 levels were elevated in biopsy samples from individuals with active celiac disease but not in those in remission on a gluten-free diet.

    Significance for Celiac Disease Patients

    The use of organoids provides a powerful new tool for understanding celiac disease at a cellular level. These models allow researchers to study the disease in ways that were not possible before, offering insights into the interactions between different cell types and the molecular mechanisms driving the immune response to gluten. The identification of IL-7 as a key player in celiac disease opens new avenues for potential therapeutic interventions. By targeting IL-7, it may be possible to develop treatments that mitigate the immune response to gluten and prevent the intestinal damage characteristic of celiac disease.

    In conclusion, this study represents a significant advancement in the understanding of celiac disease. The ability to model the disease using organoids provides a platform for developing new drugs and personalized treatments. The discovery of IL-7's role in the disease process could lead to innovative therapies that improve the quality of life for individuals with celiac disease. The findings underscore the importance of continued research and the potential for organoid models to transform our approach to studying and treating autoimmune disorders.

    Read more at: nature.com


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    Lotte18

    Thanks for posting this.  And for translating the technical medical language in Nature's article into something the average reader can digest.  Pun intended!  Do you know if IL-7 is being looked into by researchers who study MS?  RA?  How much cross pollination goes on among these researchers?  I have an aunt with MS from the same branch of the family that my celiac descends from...

    Thanks again.

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    Scott Adams

    Yes, interleukin-7 (IL-7) is indeed being studied in the context of autoimmune diseases like multiple sclerosis (MS) and rheumatoid arthritis (RA). IL-7 is a cytokine that plays a critical role in the development and maintenance of T cells, which are key players in the immune system.

    In the case of MS, research is focused on understanding how IL-7 contributes to the abnormal immune responses that target the central nervous system. Elevated levels of IL-7 have been observed in patients with MS, and researchers are investigating how this cytokine may exacerbate the disease by promoting the survival and activity of autoreactive T cells, which attack the myelin sheath around nerves.

    For RA, IL-7 is also a significant focus of research due to its role in modulating T-cell function. Studies have shown that IL-7 levels are elevated in the joints of patients with RA, contributing to the chronic inflammation characteristic of the disease. By promoting the activity of T cells in the synovial fluid of joints, IL-7 is believed to drive the ongoing inflammation and tissue damage seen in RA.

    The connection between IL-7 and these autoimmune diseases highlights its potential as a therapeutic target. Researchers are exploring ways to block or modulate IL-7 activity to develop new treatments for conditions like MS and RA.

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    Lotte18

    So perhaps, if the RA and/or MS folks come up with an experimental treatment for IL-7 first, us celiacs can apply to try that route as well.  (I assume their research grants are much larger and more consistent than ours.)

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    Scott Adams was diagnosed with celiac disease in 1994, and, due to the nearly total lack of information available at that time, was forced to become an expert on the disease in order to recover. In 1995 he launched the site that later became Celiac.com to help as many people as possible with celiac disease get diagnosed so they can begin to live happy, healthy gluten-free lives.  He is co-author of the book Cereal Killers, and founder and publisher of the (formerly paper) newsletter Journal of Gluten Sensitivity. In 1998 he founded The Gluten-Free Mall which he sold in 2014. Celiac.com does not sell any products, and is 100% advertiser supported.


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