Pathogenic mechanisms by which gluten/gliadin peptides induce inflammation in remote organs, and the extended potential harmful effects in non-celiac ADs (IMAGE)

Xia & He Publishing Inc.

Pathogenic mechanisms by which gluten/gliadin peptides induce inflammation in remote organs, and the extended potential harmful effects in non-celiac ADs

Caption

(a) Gluten is ingested and digested, reaching the gut lumen as gliadin peptides; (b) Gliadins are a prime substrate for deamidation and cross-linking by luminal transglutaminases. These post-translationally modified proteins (PTMP) increase their immunogenicity. Luminal digestive enzymes cannot further break down these protein complexes, leading to an inflammatory cascade that results in mucus disruption, dysbiosis, intestinal epithelial damage, and leaky gut; (c) Gliadin peptides and transglutaminases can potentially infiltrate through open junctions or trans-enterocytically into the lamina propria, exposing the highly immunoreactive sub-epithelium to foreign antigens or complexes; (d) In the lamina propria, dendritic cells (DCs) encounter gliadin-transglutaminase cross-linked complexes and migrate to lymph nodes as antigen-presenting cells to activate T cells. Secretion of IFNγ, IL-17, and IL-22 by Th1 and Th17 cells activates B cells, which secrete anti-tTG, anti-neo-tTG, and anti-endomysial autoantibodies (EMA); (e) Mucosal immune cells, immunogenic modified peptides, proinflammatory cytokines, autoantibodies, and small particles that escape the immune system enter the blood vessels. They can eventually reach remote organs and trigger an autoimmune response; (f) Some examples of inflammatory conditions that can be affected by the presence of gliadin peptides and transglutaminases or cross-linked complexes in peripheral organs. AD, Alzheimer’s Disease; AIH, Autoimmune Hepatitis; AIM, Autoimmune Myocarditis; AIP, Autoimmune Pericarditis; AT, Autoimmune Thyroiditis; CD, Celiac disease; DM, Dermatomyositis; GA, Gluten Ataxia; IBD, Inflammatory Bowel Diseases; IEL, intraepithelial lymphocytes.; IgA-Neph, IgA nephropathy (Berger’s disease); MS, Multiple Sclerosis; mTG, microbial transglutaminase; PA, Psoriatic Arthritis; PD, Parkinson’s Disease; RA, Rheumatoid Arthritis; T1D, Type 1 Diabetes; tTG, tissue transglutaminase.

Credit

Aaron Lerner, Carina Benzvi, Aristo Vojdani

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License

CC BY-NC

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