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-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.
Laffont
Sophie
S
Sir William Dunn School of Pathology, Oxford, UK.
Siddiqui
Karima R R
KR
Powrie
Fiona
F
D019264:Adoptive Transfer; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007108:Immune Tolerance; D007249:Inflammation; D039001:Integrin alpha Chains / Q000096:biosynthesis; D007422:Intestines / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D050697:Retinal Dehydrogenase; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis* / Q000235:genetics
D015703:Antigens, CD; D039001:Integrin alpha Chains; D011948:Receptors, Antigen, T-Cell; D053781:Transforming Growth Factor beta2; C091367:alpha E integrins; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C512722:Aldh1a2 protein, mouse; D050697:Retinal Dehydrogenase