Inflammatory Bowel Disease-Associated Gp2 Autoantibodies Inhibit Mucosal Immune Response To Adherent-Invasive Bacteria
INFLAMMATORY BOWEL DISEASES(2020)
摘要
Adherent-invasive Escherichia coli have been suggested to play a pivotal role within the pathophysiology of inflammatory bowel disease (IBD). Autoantibodies against distinct splicing variants of glycoprotein 2 (GP2), an intestinal receptor of the bacterial adhesin FimH, frequently occur in IBD patients. Hence, we aimed to functionally characterize GP2-directed autoantibodies as a putative part of IBD's pathophysiology.Ex vivo, GP2-splicing variant 4 (GP2#4) but not variant 2 was expressed on intestinal M or L cells with elevated expression patterns in IBD patients. The GP2#4 expression was induced in vitro by tumor necrosis factor (TNF)-alpha. The IBD-associated GP2 autoantibodies inhibited FimH binding to GP2#4 and were decreased in anti-TNF alpha-treated Crohn's disease patients with ileocolonic disease manifestation. In vivo, mice immunized against GP2 before infection with adherent-invasive bacteria displayed exacerbated intestinal inflammation. In summary, autoimmunity against intestinal expressed GP2#4 results in enhanced attachment of flagellated bacteria to the intestinal epithelium and thereby may drive IBD's pathophysiology.
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关键词
FimH, Crohn's disease, ulcerative colitis, M cells, L cells, anti-GP2 autoantibodies
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