Bacterial flagellin is a dominant antigen in Crohn disease.
By M. Lodes, Y. Cong, C. Elson, R. Mohamath, C. Landers, S. Targan, M. Fort, R. Hershberg. Journal of Clinical Investigation, 2004
598 citations recorded by the source corpus.
Chronic intestinal inflammation, as seen in inflammatory bowel disease (IBD), results from an aberrant and poorly understood mucosal immune response to the microbiota of the gastrointestinal tract in genetically susceptible individuals. Here we used serological expression cloning to identify commensal bacterial proteins that could contribute to the pathogenesis of IBD. The dominant antigens identified were flagellins, molecules known to activate innate immunity via Toll-like receptor 5 (TLR5), and critical targets of the acquired immune system in host defense. Multiple strains of colitic mice had elevated serum anti-flagellin IgG2a responses and Th1 T cell responses to flagellin. In addition, flagellin-specific CD4(+) T cells induced severe colitis when adoptively transferred into naive SCID mice. Serum IgG to these flagellins, but not to the dissimilar Salmonella muenchen flagellin, was elevated in patients with Crohn disease, but not in patients with ulcerative colitis or in controls. These results identify flagellins as a class of immunodominant antigens that stimulate pathogenic intestinal immune reactions in genetically diverse hosts and suggest new avenues for the diagnosis and antigen-directed therapy of patients with IBD.
Subfields: Epidemiology, Genetics
View Paper: https://www.semanticscholar.org/paper/044190ae72f6f4bae38864bba872ed73dc8aaceb
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Citations in the corpus
- Role of the Microbiota in Immunity and inflammation (2014, background): “Indeed, increased serum antibody responses against antigens derived from the microbiota are characteristic of Crohn’s disease patients (Dubinsky et al., 2006; Lodes et al., 2004).”
- Epithelial barriers in homeostasis and disease. (2010, background): “Finally, defects in innate immunity, such as those associated with abnormalities in Toll-like receptors (143–146), or defects in adaptive immunity, documented by the presence of antibodies to bacterial components (147, 148), may trigger this self-amplifying cycle of inflammation.”
- Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis (2007, background): “Associations between the response to microbial products and chronic intestinal inflammation have been noted for flagellin: both colitic mice and individuals with Crohn disease show elevated anti-flagellin serum Ig”
- TLR Signaling in the Gut in Health and Disease1 (2005, unknown): “flagellin derived from commensal bacteria (15).”
- XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease (2008, methodology): “To test whether XBP1-mediated intestinal inflammation arose from increased JNK activity in a microbiota- and cytokine-free system, we silenced XBP1 expression in the mouse IEC line MODE-K with an siRNA retrovirus (iXBP) and used flagellin and TNFa as proinflammatory stimulants (Lodes et al., 2004).”