title: Increased Th17-inducing activity of CD14+ CD163 low myeloid cells in intestinal lamina propria of patients with Crohn's disease.
abstract: OBJECTIVE
  Abnormal activity of innate immune cells and T-helper (Th) 17 cells has been implicated in the pathogenesis of autoimmune and inflammatory diseases, including Crohn's disease (CD). Intestinal innate immune (myeloid) cells have been found to induce development of Th17 cells in mice, but it is not clear if this occurs in humans or in patients with CD. We investigated whether human intestinal lamina propria cells (LPCs) induce development of Th17 cells and whether these have a role in the pathogenesis of CD.
  
  
  METHODS
  Normal intestinal mucosa samples were collected from patients with colorectal cancer and noninflamed and inflamed regions of mucosa were collected from patients with CD. LPCs were isolated by enzymatic digestion and analyzed for expression of HLA-DR, lineage markers CD14 and CD163 using flow cytometry.
  
  
  RESULTS
  Among HLA-DR(high) Lin(-) cells, we identified a subset of CD14(+) CD163(low) cells in intestinal LPCs; this subset expressed Toll-like receptor (TLR) 2, TLR4, and TLR5 mRNAs and produced interleukin (IL)-6, IL-1β, and tumor necrosis factor in response to lipopolysaccharide. In vitro co-culture with naïve T cells revealed that CD14(+) CD163(low) cells induced development of Th17 cells. CD14(+) CD163(low) cells from inflamed regions of mucosa of patients with CD expressed high levels of IL-6, IL-23p19, and tumor necrosis factor mRNAs, and strongly induced Th17 cells. CD14(+) CD163(low) cells from the noninflamed mucosa of patients with CD also had increased abilities to induce Th17 cells compared with those from normal intestinal mucosa.
  
  
  CONCLUSIONS
  CD14(+) CD163(low) cells in intestinal LPCs from normal intestinal mucosa induce differentiation of naive T cells into Th17 cells; this activity is increased in mucosal samples from patients with CD. These findings show how intestinal myeloid cell types could contribute to pathogenesis of CD and possibly other Th17-associated diseases.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ogino
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.forename: Soumik
authors.initials: S
authors.lastname: Barman
authors.forename: Hisako
authors.initials: H
authors.lastname: Kayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okuzaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Osawa
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Haraguchi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Uemura
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology*; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology*; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism*; D058504:Th17 Cells / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D053583:Interleukin-1beta; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha
keywords: 6-sulfo LacNAc; CD; CDi; CDn; Crohn’s disease; DC; Dendritic Cell; Helper T Cell; IBD; IFN; IL; Inflammatory Bowel Disease; LPC; MLN; Macrophage; NC; T-helper; TGF; TLR; TNF; Th; Toll-like receptor; dendritic cell; inflamed region of CD; inflammatory bowel disease; int; interferon; interleukin; intermediate; lamina propria cell; mRNA; mesenteric lymph node; messenger RNA; noninflamed region of CD; normal colon from colon cancer patients; slan; transforming growth factor; tumor necrosis factor