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  • Jefferson Adams

    Chronic Celiac Inflammation Permanently Changes Tissue-Resident Immunity

    Jefferson Adams
    Reviewed and edited by a celiac disease expert.

      Chronic inflammation causes permanent changes to tissue-resident immunity in celiac disease patients.

    Image: CC--vicariousdancin
    Caption: Image: CC--vicariousdancin

    Celiac.com 03/04/2019 - Tissue-resident lymphocytes play a key role in immune surveillance, but there’s not much data on how these cells respond to chronic inflammation. A team of researchers recently set out to assess how well tissue-resident lymphocytes respond to chronic inflammation. The research team included Toufic Mayassi; Kristin Ladell; Herman Gudjonson; Jamie Rossjohn; David A. Price; and Bana Jabri.

    In celiac disease, the team found that gluten-induced inflammation substantially reduced levels of naturally occurring Vγ4 +/Vδ1 + intraepithelial lymphocytes (IELs) with innate cytolytic properties and specificity for the butyrophilin-like (BTNL) molecules BTNL3/BTNL8. 

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    Creation of a new niche with reduced expression of BTNL8 and loss of Vγ4 +/Vδ1 + IELs occurred together with the expansion of gluten-sensitive, interferon-γ-producing Vδ1 + IELs bearing T cell receptors (TCRs) with a shared non-germline-encoded motif that failed to recognize BTNL3/BTNL8. 

    Eliminating dietary gluten normalized BTNL8 expression, but was not enough to restore the physiological Vγ4 +/Vδ1 + subset among TCRγδ + IELs. Together, the data show that long-term inflammation permanently changes the tissue-resident TCRγδ + IEL compartment in celiac disease. What exactly does that mean? Some of the takeaways include:

    • Innate-like Vδ1 + IELs are superseded by interferon-γ-producing Vδ1 + IELs in celiac disease
    • The Vδ1 + IEL TCR repertoire is permanently reshaped in celiac disease
    • A molecular signature defines Vδ1 + IEL expansions in active celiac disease
    • Loss of BTNL8 expression coincides with permanent loss of BTNL3/8-reactive γδ + IELs in celiac disease

    Even on a gluten-free diet, chronic inflammation causes permanent changes to the tissue-resident TCRγδ + IEL compartment in celiac patients. Further study is needed to determine the full significance of these findings.

    Read more in: CELL


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  • 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.

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