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

Intestinal CD103+ DC promote the differentiation of Foxp3+ Treg from naïve CD4+ T cells through mechanisms involving TGF‐β 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 inf...

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Bibliographic Details
Published in:European journal of immunology 2010-07, Vol.40 (7), p.1877-1883
Main Authors: Laffont, Sophie, Siddiqui, Karima R. R., Powrie, Fiona
Format: Article
Language:English
Subjects:
Adoptive Transfer
Aldehyde Dehydrogenase - biosynthesis
Aldehyde Dehydrogenase - genetics
Aldehyde Dehydrogenase 1 Family
Animals
Antigens, CD - biosynthesis
Cell Movement - immunology
Cells, Cultured
Colitis
Colitis - immunology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dendritic Cells - pathology
Immune Tolerance
Inflammation
Integrin alpha Chains - biosynthesis
Intestinal immunity
Intestines - immunology
Intestines - pathology
Lymph Nodes - pathology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Mutant Strains
Mice, Transgenic
Ontogeny
Receptors, Antigen, T-Cell - genetics
Retinal Dehydrogenase
Transforming Growth Factor beta2 - biosynthesis
Transforming Growth Factor beta2 - genetics
Treg
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Summary:Intestinal CD103+ DC promote the differentiation of Foxp3+ Treg from naïve CD4+ T cells through mechanisms involving TGF‐β 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 tgfβ2 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‐γ‐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.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.200939957