Coeliac disease (CD) is an inflammatory autoimmune disease caused by ingestion of gluten proteins, mainly gliadin. Undigested gliadin proline‐rich peptides trigger the innate and adaptive immune response, resulting in intestinal cell stress and damage. A new study by Villella et al (2019) addressing the unclear primary cause of intestinal cell stress reports that gliadin peptides inhibit the function of the chloride and bicarbonate channel CFTR, causing intestinal cell stress, which is sufficient to trigger CD symptoms. Notably, CFTR potentiators used to treat cystic fibrosis effectively rescue CFTR function and markedly ameliorate the pathology of coeliac disease.
See also: VR Villella et al (January 2019)
Coeliac disease (CD) is an inflammatory autoimmune disease affecting primarily the small intestine. The disease is common, with a prevalence of about 1 in 100, and affects individuals who express antigens HLA‐DQ2 or HLA‐DQ8 (Stamnaes & Sollid, 2015). CD is caused by oral intolerance to gluten, a group of storage proteins found in wheat, rye and barley. A key component of the gluten proteome is gliadin, which triggers a massive immune response that is exacerbated by stressed and damaged intestinal epithelial tissue. Gliadin contains proline‐rich stretches that are resistant to proteolytic degradation by intestinal proteases and are transported to the lamina propria by transcytosis after deamidated by transglutaminase 2 (TG2; Stamnaes & Sollid, 2015). In the lamina propria, deamidated gliadin peptides activate the adaptive immune response, including pathogenic CD4+ T cell that produces large amounts of IFN (interferon)‐γ and IL (interleukin)‐21 and highly disease‐specific B‐cell responses that generate IgA against TG2 (Stamnaes & Sollid, 2015).
The adaptive immune response causes epithelial cell stress, which promotes …
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