Details

Autor(en) / Beteiligte

• Junker, Yvonne
• Zeissig, Sebastian
• Kim, Seong-Jun
• Barisani, Donatella
• Wieser, Herbert
• Leffler, Daniel A
• Zevallos, Victor
• Libermann, Towia A
• Dillon, Simon
• Freitag, Tobias L
• Kelly, Ciaran P
• Schuppan, Detlef

Titel

Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4

Ist Teil von

• The Journal of experimental medicine, 2012-12, Vol.209 (13), p.2395-2408

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• 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 proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients' biopsies. Mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs. These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders.