Gut CD103+ dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction
| Autor: | Erika Mileti, Elisa Mazzini, Maria Rescigno, Marcello Chieppa, Gianluca Matteoli, Francesca Fallarino, Iliyan D. Iliev, Paolo Puccetti |
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| Přispěvatelé: | Matteoli, G., Mazzini, E., Iliev, I. D., Mileti, E., Fallarino, F., Puccetti, P., Chieppa, M., Rescigno, M. |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Administration
Oral DRAINING LYMPH-NODES T-Lymphocytes Regulatory DISEASE Mice 0302 clinical medicine T-Lymphocyte Subsets Mesenteric lymph nodes Enzyme Inhibitors Intestinal Mucosa Indoleamine 2 3-dioxygenase Cells Cultured Mice Inbred BALB C 0303 health sciences Gastroenterology FOXP3 Cell Differentiation hemic and immune systems TGF-BETA Colitis 3. Good health Cell biology medicine.anatomical_structure DIFFERENTIATION Integrin alpha Chains Ovalbumin T cell Mice Transgenic chemical and pharmacologic phenomena Biology 03 medical and health sciences Antigen INFLAMMATION Antigens CD In vivo INTESTINAL EPITHELIAL-CELLS RETINOIC-ACID GENERATION CONVERSION Immune Tolerance medicine Animals Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Immunity Mucosal 030304 developmental biology Dendritic Cells In vitro Mice Inbred C57BL T cell differentiation Immunology 030215 immunology |
| Zdroj: | Gut |
| Popis: | Objective CD103 + gut dendritic cells (DCs) have been shown to be required for de novo conversion of adaptive T regulatory (Treg) cells. Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in tryptophan catabolism that is expressed by DCs isolated from tumour-draining lymph nodes. IDO-expressing DCs sustain and differentiate Tregs. The aim of this study was to investigate the expression and the possible physiological role of IDO in the tolerogenic properties of intestinal DCs. Design The expression level of IDO in CD103 + and CD103 − DCs was analysed by qRT-PCR, western blot and immunofluorescence. CD103 + and CD103 − DCs were sorted from mesenteric lymph nodes (MLNs) and the small intestinal lamina propria, and the role of IDO in the conversion of Tregs and Th effector cell development was evaluated via specific inhibition or gene deletion. Oral tolerance, experimental colitis and T cell differentiation in vivo were assessed upon IDO inactivation. Results We show that, primarily, CD103 + but not CD103 − gut DCs express IDO whose inhibition results in reduced CD4 + Foxp3 + T regulatory cell conversion and enhanced T cell proliferation. When IDO was inhibited or genetically deleted there was an increase in Th1 and Th17 differentiation both in vitro and in vivo. Finally, in vivo IDO blockade affected the development of Tregs specific for orally administered antigens, impaired oral tolerance induction and exacerbated colitis. Conclusions We identified a new IDO-dependent pathway leading to acquisition of tolerogenic functions in mucosal CD103-expressing DCs, indicating IDO as a possible therapeutic target for gut disorders. |
| Databáze: | OpenAIRE |
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