title: Aberrant plasmacytoid dendritic cell distribution and function in patients with Crohn's disease and ulcerative colitis.
abstract: Dendritic cell (DC) function is believed to be of critical importance for the pathogenesis of inflammatory bowel disease (IBD). To date, most research in animal models and the few human data available is restricted to myeloid DC, while plasmacytoid DC (pDC) capable of controlling both innate and adaptive immune responses have not yet been investigated systematically in human Crohn's disease (CD) or ulcerative colitis (UC). CD11c(-) , CD303(+) /CD304(+) and CD123(+) pDC from peripheral blood (n = 90), mucosal tissue (n = 28) or mesenteric lymph nodes (n = 40) (MLNs) of patients with UC and CD or controls were purified and cultured. Thereafter, pDC were enumerated, phenotyped and cytokine secretion measured by flow cytometry (FACS), immunohistochemistry and/or cytometric bead array, respectively. Interferon (IFN)-α secretion following cytosine phosphatidyl guanine (CpG) A oligodeoxynucleotide (ODN) 2216 (5'-GGGGGACGATCGTCGGGGGG-3') stimulation was assessed by enzyme-linked immunosorbent assay (ELISA). We found a significantly higher frequency of pDC in the inflamed colonic mucosa and MLN of IBD patients. Moreover, the fraction of CD40 and CD86 expressing cultured peripheral blood pDC was significantly higher in flaring UC and CD patients and their secretion of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 were increased significantly compared with controls. In contrast, the IFN-α secretion of peripheral blood pDC isolated from flaring IBD, particularly in UC patients, was reduced significantly compared with controls. Our data suggest an aberrant distribution and function of pDC in IBD, contrary to their generally implicated role as inducers of tolerance. We speculate that the impaired IFN-α secretion may relate to the hypothesized defect in innate immunity in IBD and could also impact upon the generation of regulatory T cells (T(reg) ).
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology Department of Surgery General Internal Medicine Outpatient Clinic, Charité Medical Center - Virchow Hospital, Medical School of the Humboldt-University of Berlin, 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: O
authors.initials: O
authors.lastname: Guckelberger
authors.forename: A
authors.initials: A
authors.lastname: Pascher
authors.forename: C
authors.initials: C
authors.lastname: Grötzinger
authors.forename: I
authors.initials: I
authors.lastname: Przesdzing
authors.forename: Y
authors.initials: Y
authors.lastname: Dörffel
authors.forename: J
authors.initials: J
authors.lastname: Schmitz
authors.forename: S
authors.initials: S
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D003093:Colitis, Ulcerative / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000032:analysis / Q000096:biosynthesis; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; D016898:Interferon-alpha; D015850:Interleukin-6; D016209:Interleukin-8; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha