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• W2092748647 abstract "When coeliac disease is referred to as an inflammatory disorder, this may detract from its true nature. Activation of innate and adaptive immunity takes place in the mucosal lesion, but the tissue reaction is not that of classical inflammation. In fact, coeliac disease contrasts strikingly with typical inflammatory bowel disorders such as ulcerative colitis and Crohn's disease. The coeliac lesion apparently reflects, in the main, immune-driven remodelling of mucosal architecture with only a minor inflammatory component – initially most likely resulting from innate signals. Complement split products might be one of several potential initial hits that lead to activation of lamina propria and epithelial cells with release of mediators such as interleukin-15. This cytokine appears to stimulate potentially pathogenic intraepithelial lymphocytes. In genetically susceptible individuals, such early innate events could turn into persistent pathogenic signalling with subsequent adaptive cellular and humoral immunopathology resulting in a chronic lesion. Nevertheless, mucosal homeostasis is surprisingly well preserved as signified by the remarkable dominance of plasma cells that produce dimeric immunoglobulin A as a basis for enhanced secretory immunity. This shows that the microvascular endothelium in the lesion largely maintains its ‘gatekeeper’ function for mucosal immune cells – in striking contrast to the ‘promiscuous’ situation in inflammatory bowel disease. Altogether, a two-signal model is emerging for the pathogenesis of coeliac disease – signal 1 generated by innate immunity and signal 2 by adaptive immunity. Hence, there is currently an increased focus on immune activation in the epithelial compartment rather than on changes in the microvasculature as a basis for classical inflammation." @default.
• W2092748647 created "2016-06-24" @default.
• W2092748647 creator A5042575652 @default.
• W2092748647 date "2006-06-01" @default.
• W2092748647 modified "2023-09-25" @default.
• W2092748647 title "The changing immunological paradigm in coeliac disease" @default.
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• W2092748647 doi "https://doi.org/10.1016/j.imlet.2006.03.004" @default.
• W2092748647 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16647763" @default.
• W2092748647 hasPublicationYear "2006" @default.
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