RRC ID 45523
Author Okumura R, Kurakawa T, Nakano T, Kayama H, Kinoshita M, Motooka D, Gotoh K, Kimura T, Kamiyama N, Kusu T, Ueda Y, Wu H, Iijima H, Barman S, Osawa H, Matsuno H, Nishimura J, Ohba Y, Nakamura S, Iida T, Yamamoto M, Umemoto E, Sano K, Takeda K.
Title Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia.
Journal Nature
Abstract Colonic epithelial cells are covered by thick inner and outer mucus layers. The inner mucus layer is free of commensal microbiota, which contributes to the maintenance of gut homeostasis. In the small intestine, molecules critical for prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti-microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have been identified. Although there are mucus layers providing physical barriers against the large number of microbiota present in the large intestine, the mechanisms that separate bacteria and colonic epithelia are not fully elucidated. Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively expressed in epithelial cells at the uppermost layer of the large intestinal gland, was secreted into the lumen and bound flagellated bacteria including Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner mucus layer and many flagellated bacteria invaded epithelia. Lypd8(-/-) mice were highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the bacterial-free state of the inner mucus layer and ameliorated DSS-induced intestinal inflammation in Lypd8(-/-) mice. Lypd8 bound to flagella and suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of intestinal bacteria and epithelial cells in the colon to preserve intestinal homeostasis.
Volume 532(7597)
Pages 117-21
Published 2016-4-7
DOI 10.1038/nature17406
PII nature17406
PMID 27027293
MeSH Animals Bacterial Adhesion Caco-2 Cells Cell Line Colitis / chemically induced Colitis / drug therapy Colitis / genetics Colon / microbiology* Dextran Sulfate Epithelium / microbiology* Female Flagella* GPI-Linked Proteins / deficiency GPI-Linked Proteins / genetics GPI-Linked Proteins / metabolism* Gram-Negative Bacteria / drug effects Gram-Negative Bacteria / metabolism Gram-Negative Bacteria / pathogenicity Gram-Negative Bacteria / physiology* Homeostasis Humans Inflammation / chemically induced Inflammation / drug therapy Inflammation / genetics Intestinal Mucosa / cytology Intestinal Mucosa / metabolism Intestinal Mucosa / microbiology* Male Mice Proteus mirabilis / drug effects Proteus mirabilis / metabolism Proteus mirabilis / pathogenicity Symbiosis
IF 42.779
DNA material Flag-tagged Lypd8 in pcDNA3.1(+) (RDB14269) Flag-tagged LOC69864 in pcDNA3.1(+) (RDB14270).