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Nature. 2016 Apr 7;532(7597):117-21. doi: 10.1038/nature17406. Epub 2016 Mar 30.

Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia.

Author information

1
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.
2
Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
3
Department of Microbiology and Infection Control, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
4
Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
5
Department of Bacteriology, Okayama University Graduate School of Medicine, Okayama 700-8558, Japan.
6
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
7
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
8
Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
9
Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
10
Laboratory of Immunoparasitology, Research Institute for Microbial Diseases, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.

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.

PMID:
27027293
DOI:
10.1038/nature17406
[Indexed for MEDLINE]

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