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

2010; Wiley; Volume: 40; Issue: 7 Linguagem: Inglês

10.1002/eji.200939957

1521-4141

Sophie Laffont, Karima R.R. Siddiqui, Fiona Powrie,

Cancer Immunotherapy and Biomarkers

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.