Characterization of colonic and mesenteric lymph node dendritic cell subpopulations in a murine adoptive transfer model of inflammatory bowel disease

John Karlis, Irmeli Penttila, Tuyet B. Tran, Ben Jones, Silvia Nobbs, Heddy Zola, Inge E A Flesch

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Ulcerative colitis and Crohn's disease, collectively termed inflammatory bowel diseases (IBD), are chronic inflammatory diseases of the intestine that afflict more than 4 million people worldwide. Intestinal inflammation is characterized by an abnormal mucosal immune response to normally harmless antigens in the gut flora. In Crohn's disease, the pathogenic mucosal immune response is a typical T helper (TH1) type cell response, whereas ulcerative colitis is predominantly associated with a TH2 response. We are interested in the role of dendritic cells in early immunologic events leading to T cell activation and chronic intestinal inflammation. Using a murine adoptive transfer model of IBD, we found an accumulation of dendritic cells in colon and mesenteric lymph nodes during the early stage of IBD before the appearance of epithelial lesions and tissue degradation. In situ immunostaining and flow-cytometric analysis revealed that approximately 50% of colonic dendritic cells were CD11b+ B220- myeloid dendritic cells and 50% expressed the CD11b- B220+ plasmacytoid phenotype. In corresponding mesenteric lymph nodes, approximately 16% were plasmacytoid dendritic cells. Colonic myeloid dendritic cells were shown to express the co-stimulatory molecule CD40. Both, colonic myeloid and plasmacytoid dendritic cells released interferon-α in situ and stimulated T cell proliferation ex vivo. Our results show that dendritic cells can mature in the intestine without migrating to mesenteric lymph nodes. Mature intestinal dendritic cells may form a nucleation site for a local T cell response and play an important role in the pathogenesis of IBD.

Original languageEnglish
Pages (from-to)834-847
Number of pages14
JournalInflammatory bowel diseases
Volume10
Issue number6
DOIs
Publication statusPublished - 1 Nov 2004

Keywords

  • Autoimmunity
  • Colitis
  • Cytokines
  • Dendritic cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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