AsianScientist (Jun. 2, 2016) – Researchers in Japan have discovered the mechanism by which a protein called Lypd8 defends the body from inflammation—it binds to the bacterium’s tail and stops it in its tracks. This finding, published in Nature, may lead to the development of drugs for ulcerative colitis.
Dysfunction of the intestinal mucosal barrier is thought to a major cause of inflammatory bowel disease. In genetically-modified mice in which the intestinal mucosal barrier is defective, bacteria invade the colonic mucosa and cause high susceptibility to intestinal inflammation. Clearly, this mucosal barrier provides a protective function, but the mechanism by which it inhibits bacterial invasion remains unclear.
The research team, led by Dr. Ryu Okumura and Professor Kiyoshi Takeda from the Osaka University Graduate School of Medicine, focused on Ly6/Plaur domain containing 8 (Lypd8), a highly glycosylated GPI-anchored protein that is selectively expressed in colonic epithelial cells and shed into the intestinal lumen.
Patients with ulcerative colitis were found to have a much lower expression of Lypd8 in the colon epithelium. In Lypd8-deficient mice, flagellated bacteria such as Proteus and Escherichia were able to rapidly invade the colonic mucosa. And when exposed to dextran sulfate sodium (DSS), a chemical which induces intestinal inflammation, Lypd8-deficient mice showed more severe DSS-induced colitis compared to wild-type mice.
In laboratory studies, Lypd8 bound to the flagellum (tail) of bacteria grown on semisolid agar plates. This mechanism is believed to be how Lypd8 inhibits bacterial motility and the subsequent invasion of colonic epithelia by bacteria in their human hosts.
The article can be found at: Okumura et al. (2016) Lypd8 Promotes the Segregation of Flagellated Microbiota and Colonic Epithelia.
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Source: Osaka University; Photo: Shutterstock.
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