title: Relationship between human intestinal dendritic cells, gut microbiota, and disease activity in Crohn's disease.
abstract: BACKGROUND
  Altered intestinal dendritic cell (DC) function underlies dysregulated T-cell responses to bacteria in Crohn's disease (CD) but it is unclear whether composition of the intestinal microbiota impacts local DC function. We assessed the relationship between DC function with disease activity and intestinal microbiota in patients with CD.
  
  
  METHODS
  Surface expression of Toll-like receptor (TLR)-2, TLR-4, and spontaneous intracellular interleukin (IL)-10, IL-12p40, IL-6 production by freshly isolated DC were analyzed by multicolor flow cytometry of cells extracted from rectal tissue of 10 controls and 28 CD patients. Myeloid DC were identified as CD11c(+) HLA-DR(+lin-/dim) cells (lin = anti-CD3, CD14, CD16, CD19, CD34). Intestinal microbiota were analyzed by fluorescent in situ hybridization of fecal samples with oligonucleotide probes targeting 16S rRNA of bifidobacteria, bacteroides-prevotella, C. coccoides-E. rectale, and Faecalibacterium prausnitzii.
  
  
  RESULTS
  DC from CD produced higher amounts of IL-12p40 and IL-6 than control DC. IL-6(+) DC were associated with the CD Activity Index (r = 0.425; P = 0.024) and serum C-reactive protein (CRP) (r = 0.643; P = 0.004). DC expression of TLR-4 correlated with disease activity. IL-12p40(+) DC correlated with ratio of bacteroides: bifidobacteria (r = 0.535, P = 0.003). IL-10(+) DC correlated with bifidobacteria, and IL-6(+) DC correlated negatively with F. prausnitzii (r = -0.50; P = 0.008). The amount of TLR-4 on DC correlated negatively with the concentration of F. prausnitzii.
  
  
  CONCLUSIONS
  IL-6 production by intestinal DC is increased in CD and correlates with disease activity and CRP. Bacterially driven local IL-6 production by intestinal DC may overcome regulatory activity, resulting in unopposed effector function and tissue damage. Intestinal DC function may be influenced by the composition of the commensal microbiota.
authors: Antigen Presentation Research Group, Imperial College London, St Mark's Hospital, London, UK.
authors: S C
authors: SC
authors: Ng
authors: J L
authors: JL
authors: Benjamin
authors: N E
authors: NE
authors: McCarthy
authors: C R H
authors: CR
authors: Hedin
authors: A
authors: A
authors: Koutsoumpas
authors: S
authors: S
authors: Plamondon
authors: C L
authors: CL
authors: Price
authors: A L
authors: AL
authors: Hart
authors: M A
authors: MA
authors: Kamm
authors: A
authors: A
authors: Forbes
authors: S C
authors: SC
authors: Knight
authors: J O
authors: JO
authors: Lindsay
authors: K
authors: K
authors: Whelan
authors: A J
authors: AJ
authors: Stagg
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D003424:Crohn Disease / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D003713:Dendritic Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D055815:Young Adult
chemical_list: D019013:CD40 Antigens; D015850:Interleukin-6; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D002097:C-Reactive Protein