RESUMO
Mucosal dendritic cells (DCs) in the intestine acquire the unique capacity to produce retinoic acid (RA), a vitamin A metabolite that induces gut tropism and regulates the functional differentiation of the T cells they prime. Here, we identified a stromal cell (SC) population in the intestinal lamina propria (LP), which is capable of inducing RA production in DCs in a RA- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent fashion. Unlike DCs, LP SCs constitutively expressed the enzymatic machinery to produce RA even in the absence of dietary vitamin A, but were not able to do so in germ-free mice implying regulation by microbiota. Interestingly, DCs promoted GM-CSF production by the SCs indicating a two-way cross-talk between both cell types. Furthermore, RA-producing LP SCs and intestinal DCs localized closely in vivo suggesting that the interactions between both cell types might have an important role in the functional education of migratory DCs and therefore in the regulation of immune responses toward oral and commensal antigens.
Assuntos
Células Dendríticas/imunologia , Mucosa/imunologia , Células Estromais/imunologia , Linfócitos T/imunologia , Tretinoína/metabolismo , Animais , Comunicação Celular , Diferenciação Celular , Movimento Celular , Células Cultivadas , Dieta , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Imunidade nas Mucosas , Imunomodulação , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tretinoína/imunologiaAssuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ibuprofeno/efeitos adversos , Adalimumab , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antirreumáticos/administração & dosagem , Humanos , Ibuprofeno/administração & dosagem , Masculino , Pessoa de Meia-IdadeRESUMO
Dendritic cells (DCs) are strong activators of primary T cell responses. Their priming ability is acquired upon encounter with maturation stimuli. To identify the genes that are differentially expressed upon maturation induced by exposure to Gram-negative bacteria, a kinetic study of DC gene expression was done with microarrays representing 11,000 genes and ESTs (expressed sequence tags). Approximately 3000 differentially expressed transcripts were identified. We found that functional interleukin 2 (IL-2) mRNA, which gave rise to IL-2 production, was transiently up-regulated at early time-points after bacterial encounter. In contrast, macrophages did not produce IL-2 upon bacterial stimulation. Thus, IL-2 is an additional key cytokine that confers unique T cell stimulatory capacity to DCs.