{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:59:05Z","timestamp":1792407545623,"version":"4.4.0"},"reference-count":49,"publisher":"Rockefeller University Press","issue":"13","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,12,17]]},"abstract":"<jats:p>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 \u03b1-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\u2013MD2\u2013CD14 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\u2019 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.<\/jats:p>","DOI":"10.1084\/jem.20102660","type":"journal-article","created":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T08:40:46Z","timestamp":1354610446000},"page":"2395-2408","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":563,"title":["Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4"],"prefix":"10.1084","volume":"209","author":[{"given":"Yvonne","family":"Junker","sequence":"first","affiliation":[{"name":"Division of Gastroenterology 1 and 2"},{"name":"Proteomics and Genomics Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 1 and 2"},{"name":"Department of General Pediatrics 3 and 4"},{"name":"Department of Internal Medicine I, University Medical Center Schleswig-Holstein Kiel, 24105 Kiel, Germany 3 and 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Milano-Bicocca, 20126 Milan, Italy 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Wieser","sequence":"additional","affiliation":[{"name":"German Research Center for Food Chemistry, 85748 Garching, Germany 6"},{"name":"Hans-Dieter-Belitz-Institute for Cereal Grain Research, 85354 Freising, Germany 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Leffler","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology 1 and 2"},{"name":"Proteomics and Genomics Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Zevallos","sequence":"additional","affiliation":[{"name":"Division of Molecular and Translational Medicine, Department of Medicine I, Johannes Gutenberg University, 55131 Mainz, Germany 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Towia A.","family":"Libermann","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology 1 and 2"},{"name":"Proteomics and Genomics Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Dillon","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology 1 and 2"},{"name":"Proteomics and Genomics Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias L.","family":"Freitag","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology 1 and 2"},{"name":"Proteomics and Genomics Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 1 and 2"},{"name":"Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, 00014 Helskini, Finland 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