title: Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia.
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.
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Okumura
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurakawa
authors.affiliation: Department of Microbiology and Infection Control, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Kayama
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Motooka
authors.affiliation: Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Bacteriology, Okayama University Graduate School of Medicine, Okayama 700-8558, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Gotoh
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Naganori
authors.initials: N
authors.lastname: Kamiyama
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kusu
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Microbiology and Infection Control, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Iijima
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Soumik
authors.initials: S
authors.lastname: Barman
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Osawa
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuno
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.affiliation: Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohba
authors.affiliation: Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Iida
authors.affiliation: Laboratory of Immunoparasitology, Research Institute for Microbial Diseases, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Umemoto
authors.affiliation: Department of Microbiology and Infection Control, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sano
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D018938:Caco-2 Cells; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics; D003106:Colon / Q000382:microbiology*; D016264:Dextran Sulfate; D004848:Epithelium / Q000382:microbiology*; D005260:Female; D005407:Flagella; D058851:GPI-Linked Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D051379:Mice; D011513:Proteus mirabilis / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity; D013559:Symbiosis
chemical_list: D058851:GPI-Linked Proteins; C000607339:LYPD8 protein, human; C000607338:Ly6-PLAUR domain containing 8 protein, mouse; D016264:Dextran Sulfate