Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 40, Issue 7, Pages 1877-1883Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.200939957
Keywords
Colitis; DC; Intestinal immunity; Ontogeny; Treg
Categories
Funding
- Wellcome Trust
- Medical Research Council
Ask authors/readers for more resources
Intestinal CD103(+) DC promote the differentiation of Foxp3(+) Treg from naive 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 tgf beta 2 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available