title: Identification of a human intestinal myeloid cell subset that regulates gut homeostasis.
abstract: Inappropriate activation of T helper (Th) cells, such as Th1 and Th17 cells, is implicated in the pathogenesis of chronic inflammatory disorders including ulcerative colitis (UC). CX3CR1highmacrophages contribute to intestinal homeostasis through various mechanisms in mice. However, whether mononuclear phagocytes with regulatory functions are present in the human colon is not clearly defined. We investigated whether innate myeloid cells that suppress activation of effector T cells exist in the human intestinal mucosa. Among intestinal lamina propria cells, Lin-HLA-DRhighCD14+CD163highcells were subdivided into CD160lowand CD160highcells. Both subsets produced high levels of IL-10. CD163highCD160highcells suppressed effector T cell proliferation, whereas CD163highCD160lowcells induced Th17 differentiation. Patients with UC exhibited increased numbers of CD163highCD160lowcells, while showing profoundly decreased numbers of CD163highCD160highcells. In this context, CD163highCD160highcells had higher CD80/CD86 expression and lower IL10RB expression, and these cells did not suppress effector T cell proliferation. The CD163highCD160highsubset in normal intestinal mucosa inhibits inappropriate Th1/Th17 responses through suppression of their proliferation, and its number and suppressive activity are impaired in patients with UC. These findings indicate how human innate immune cells might prevent UC development.
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine and.|Laboratory of Mucosal Immunology, 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: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine and.|Laboratory of Mucosal Immunology, 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: DNA-Chip Developmental Center for Infectious Diseases, Research Institute for Microbial Diseases and.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okuzaki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ogino
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, 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, Suita, 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, Suita, Osaka 565-0871, Japan.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine and.|Laboratory of Mucosal Immunology, 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: D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D049109:Cell Proliferation; D058851:GPI-Linked Proteins / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D007422:Intestines / Q000166:cytology* / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C114505:CD160 protein, human; D000098902:CD163 Antigen; D058851:GPI-Linked Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic
keywords: human intestinal lamina propria; inflammatory bowel disease; innate immunity; mononuclear phagocytes