Intestinal inflammation abrogates the tolerogenic properties of MLN CD103+ dendritic cells

Eur J Immunol. 2010 Jul;40(7):1877-83. doi: 10.1002/eji.200939957.

Abstract

Intestinal CD103(+) DC promote the differentiation of Foxp3(+) Treg from naïve CD4(+) T cells through mechanisms involving TGF-beta and the dietary metabolite, retinoic acid (RA). In this study, we have analysed whether the specialised features of CD103(+) DC are conserved in colitis. Our results show that inflammation dampens the tolerogenic properties of MLN CD103(+) DC, which is associated with lower expression of tgfbeta2 and aldh1a2. Accordingly, CD103(+) DC taken from colitic mice are impaired in their ability to induce Foxp3(+) Treg and instead favour the emergence of IFN-gamma-producing CD4(+) T cells compared with their steady-state counterparts. BrdU-labelling studies and analysis of ontogeny markers show that CD103(+) DC from steady-state and colitic settings retain similar subset composition and developmental pathways. These results indicate that MLN CD103(+) DC are not hard-wired to promote tolerance but can adapt to environmental conditions. The inflammatory properties of MLN CD103(+) DC in colitic mice may reflect defective gut tolerogenic conditioning or altered migratory pathways and raise the possibility that migratory DC populations contribute to the pathogenesis of inflammatory bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Aldehyde Dehydrogenase / biosynthesis*
  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase 1
  • Animals
  • Antigens, CD / biosynthesis
  • Cell Movement / immunology
  • Cells, Cultured
  • Colitis / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Immune Tolerance
  • Inflammation
  • Integrin alpha Chains / biosynthesis
  • Intestines / immunology
  • Intestines / pathology
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics
  • Retinal Dehydrogenase
  • Transforming Growth Factor beta2 / biosynthesis*
  • Transforming Growth Factor beta2 / genetics

Substances

  • Aldehyde Dehydrogenase 1
  • Antigens, CD
  • Integrin alpha Chains
  • Receptors, Antigen, T-Cell
  • Transforming Growth Factor beta2
  • alpha E integrins
  • Aldehyde Dehydrogenase
  • Aldh1a2 protein, mouse
  • Retinal Dehydrogenase