title: Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells.
abstract: BACKGROUND
  Breakdown of tolerance against the commensal microflora is believed to be a major factor in the pathogenesis of inflammatory bowel disease (IBD). Dendritic cells (DC) have been implicated in this process in various animal models, but data on human DC in IBD are very limited.
  
  
  OBJECTIVE
  To characterise plasmacytoid DC (PDC) and myeloid DC (MDC) in patients with active versus inactive IBD and healthy controls.
  
  
  METHODS
  Peripheral blood was obtained from 106 patients (Crohn's disease (CD) n=49, ulcerative colitis (UC) n=57) and healthy controls (n=19). Disease activity was scored using the modified Truelove Witts (MTWSI) for UC and the Harvey Bradshaw severity indices (HBSI) for CD. Four colour flow cytometric analysis was used to identify, enumerate, and phenotype DC. DC from patients with acute flare ups and healthy controls were cultured and stimulated with CpG ODN 2006 or lipopolysaccharide (LPS).
  
  
  RESULTS
  IBD patients in remission (PDC UC, 0.39%; CD, 0.35%; MDC-1 UC, 0.23%; CD, 0.22% of PBMC) have slightly lower numbers of circulating DC compared with healthy controls (PDC 0.41%, MDC-1 0.25% of PBMC). In acute flare ups IBD patients experience a significant drop of DC (PDC UC, 0.04%; CD, 0.11%; MDC-1 UC, 0.11%; CD, 0.14% of PBMC) that correlates with disease activity (correlation coefficients: PDC MTWSI, 0.93; HBSI, 0.79; MDC-1 MTWSI, 0.75; HBSI, 0.81). Moreover, both express alpha4beta7 integrin and display an immature phenotype. Freshly isolated PDC and MDC-1 from untreated flaring IBD patients express higher baseline levels of CD86 which increases further in culture and upon stimulation compared with healthy controls.
  
  
  CONCLUSIONS
  IBD patients lack immature blood DC during flare ups which possibly migrate to the gut. An aberrant response to microbial surrogate stimuli suggests a disturbed interaction with commensals.
authors.affiliation: Charité Medical Centre-Virchow Hospital, Medical School of the Humboldt-University, Department of Medicine, Division of Hepatology & Gastroenterology, D-13344 Berlin, Germany. daniel.baumgart@charite.de
authors.forename: D C
authors.initials: DC
authors.lastname: Baumgart
authors.forename: D
authors.initials: D
authors.lastname: Metzke
authors.forename: J
authors.initials: J
authors.lastname: Schmitz
authors.forename: A
authors.initials: A
authors.lastname: Scheffold
authors.forename: A
authors.initials: A
authors.lastname: Sturm
authors.forename: B
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: A U
authors.initials: AU
authors.lastname: Dignass
mesh_terms: D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD / Q000097:blood; D051940:B7-2 Antigen; D002454:Cell Differentiation; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D003713:Dendritic Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D016014:Linear Models; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D022423:Myeloid Cells / Q000473:pathology*; D012074:Remission Induction; D012720:Severity of Illness Index
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins