Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4
Beth Israel Deaconess Medical Center · Harvard University · +3 more institutions
Abstract
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 and elicit release of…
Citation impact
- FWCI
- 25.75
- Percentile
- 100%
- References
- 55
Authors
12Topics & keywords
- Immune system
- TLR4
- Immunology
- Innate immune system
- Proinflammatory cytokine
- Inflammation
- Acquired immune system
- Toll-like receptor
- Good health and well-being