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

Abstract

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, CD1031 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. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.