| First Author | Chen X | Year | 2008 |
| Journal | Am J Pathol | Volume | 173 |
| Issue | 6 | Pages | 1647-56 |
| PubMed ID | 18974296 | Mgi Jnum | J:143927 |
| Mgi Id | MGI:3829344 | Doi | 10.2353/ajpath.2008.080487 |
| Citation | Chen X, et al. (2008) Fc gamma receptor signaling in mast cells links microbial stimulation to mucosal immune inflammation in the intestine. Am J Pathol 173(6):1647-56 |
| abstractText | 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. |
