0000000001070917
AUTHOR
Tobias L. Freitag
Testing safety of germinated rye sourdough in a celiac disease model based on the adoptive transfer of prolamin-primed memory T cells into lymphopenic mice.
The current treatment for celiac disease is strict gluten-free diet. Technical processing may render gluten-containing foods safe for consumption by celiac patients, but so far in vivo safety testing can only be performed on patients. We modified a celiac disease mouse model to test antigenicity and inflammatory effects of germinated rye sourdough, a food product characterized by extensive prolamin hydrolysis. Lymphopenic Rag1−/− or nude mice were injected with splenic CD4+CD62L−CD44high-memory T cells from gliadin- or secalin-immunized wild-type donor mice. We found that: 1) Rag1−/− recipients challenged with wheat or rye gluten lost more body weight and developed more severe histological…
Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4
Ingestion of wheat, barley, or rye triggers small intestinal inflammation in patients with celiac disease. Specifically, the storage proteins of these cereals (gluten) elicit an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition. This well-defined role of adaptive immunity contrasts with an ill-defined component of innate immunity in celiac disease. We identify the α-amylase/trypsin inhibitors (ATIs) CM3 and 0.19, pest resistance molecules in wheat, as strong activators of innate immune responses in monocytes, macrophages, and dendritic cells. ATIs engage the TLR4–MD2–CD14 complex and lead to up-regulation of maturation markers a…