Colonic lamina propria dendritic cells in mice with CD4+ T cell-induced colitis

Eur J Immunol. 2003 Apr;33(4):1073-83. doi: 10.1002/eji.200323518.


CD11c(+) (F4/80(-) CD68(-)) dendritic cells (DC) in the colonic lamina propria (cLP) of normal and immunodeficient (RAG1(-/-)) C57BL/6 (B6) mice show high surface expression of MHC class I/II molecules and CD1d, and low surface expression of CD40, CD80, CD86 costimulator molecules. CD4(+) alpha beta T cells from normal or MHC class II-deficient B6 mice transferred into congenic RAG1(-/-) hosts induce a progressive, lethal colitis. Concomitant with colitis development, DC in the inflamed cLP increase in number and up-regulate surface expression of CD1d, MHC class II molecules and CD40, CD80, CD86 costimulator molecules. cLP DC from non-transplanted (healthy) and transplanted (diseased) mice produce similar amounts of IL-12 p70 and IL-10 in response to CD40 signaling, but the inducible IL-12 p40 release is 5-15-fold higher in mice with colitis than in non-transplanted mice. Binding of IL-12 p40 to p19 generates IL-23. Freshly isolated cLP lymphocytes (cLPL) from transplanted, diseased mice express 3-10-fold more p19 transcripts than cLPL from non-transplanted, healthy mice. p19 expression by cLPL is further up-regulated in response to CD40 ligation. Freshly isolated cLP DC from transplanted mice with colitis (but not from non-transplanted controls) stimulate IFN-gamma (but not IL-4 or IL-13) release by co-cultured NKT cells. Incolitis, DC accumulate in the cLP, show an activated surface phenotype, up-regulate IL-12 p40 and p19 expression, and 'spontaneously' stimulate NKT-like cells. cLP DC may be interesting targets for novel therapeutic approaches to modulate mucosal T cell responses in situ.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / transplantation
  • Cells, Cultured
  • Colitis / immunology*
  • Colitis / pathology
  • Colon / anatomy & histology
  • Colon / cytology
  • Colon / immunology*
  • Cytokines / metabolism
  • Dendritic Cells / classification
  • Dendritic Cells / immunology*
  • Genes, RAG-1
  • Immunophenotyping
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Interferon-gamma / metabolism
  • Interleukin-12 / biosynthesis
  • Interleukin-12 Subunit p40
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / physiology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Killer Cells, Natural / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Subunits / biosynthesis


  • Cytokines
  • Il23a protein, mouse
  • Interleukin-12 Subunit p40
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Protein Subunits
  • Interleukin-12
  • Interferon-gamma