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.

Junker, Y., Zeissig, S., Kim, S., Barisani, D., Wieser, H., Leffler, D., et al. (2012). Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. JOURNAL OF EXPERIMENTAL MEDICINE, 209(13), 2395-2408 [10.1084/jem.20102660].

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

BARISANI, DONATELLA;
2012

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 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.
Articolo in rivista - Articolo scientifico
Animals; Triticum; HEK293 Cells; Humans; Hordeum; Amino Acid Sequence; Immunity, Innate; Mice; Plant Proteins; Gliadin; Toll-Like Receptor 4; Mice, Knockout; Trypsin Inhibitors; Myeloid Differentiation Factor 88; Molecular Sequence Data; Mice, Inbred C3H; Mice, Inbred C57BL; Celiac Disease; Sequence Homology, Amino Acid; Signal Transduction; Cell Line; U937 Cells
English
2012
209
13
2395
2408
none
Junker, Y., Zeissig, S., Kim, S., Barisani, D., Wieser, H., Leffler, D., et al. (2012). Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. JOURNAL OF EXPERIMENTAL MEDICINE, 209(13), 2395-2408 [10.1084/jem.20102660].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/48823
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