title: Fc gamma receptor signaling in mast cells links microbial stimulation to mucosal immune inflammation in the intestine.
abstract: Microbes and microbial products are closely associated with the pathogenesis of inflammatory bowel disease (IBD); however, the mechanisms behind this connection remain unclear. It has been previously reported that flagellin-specific antibodies are increased in IBD patient sera. As mastocytosis is one of the pathological features of IBD, we hypothesized that flagellin-specific immune responses might activate mast cells that then contribute to the initiation and maintenance of intestinal inflammation. Thirty-two colonic biopsy samples were collected from IBD patients. A flagellin/flagellin-specific IgG/Fc gamma receptor I complex was identified on biopsied mast cells using both immunohistochemistry and co-immunoprecipitation experiments; this complex was shown to co-localize on the surfaces of mast cells in the colonic mucosa of patients with IBD. In addition, an ex vivo study showed flagellin-IgG was able to bind to human mast cells. These cells were found to be sensitized to flagellin-specific IgG; re-exposure to flagellin induced the mast cells to release inflammatory mediators. An animal model of IBD was then used to examine flagellin-specific immune responses in the intestine. Mice could be sensitized to flagellin, and repeated challenges with flagellin induced an IBD-like T helper 1 pattern of intestinal inflammation that could be inhibited by pretreatment with anti-Fc gamma receptor I antibodies. Therefore, flagellin-specific immune responses activate mast cells in the intestine and play important roles in the pathogenesis of intestinal immune inflammation.
authors.affiliation: Brain Body Institute, McMaster University, Ontario, Canada.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Bai-Sui
authors.initials: BS
authors.lastname: Feng
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Zheng
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Liao
authors.forename: Jasmine
authors.initials: J
authors.lastname: Chong
authors.forename: Shang-Guo
authors.initials: SG
authors.lastname: Tang
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005408:Flagellin / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D017452:Receptors, IgG; D005408:Flagellin