A synthetic peptide homologous to il-10 functional domain induces monocyte differentiation to tgf-beta plus tolerogenic dendritic cells
Autor: | Juan Carlos Aguillón, Barbara Pesce, Christian Larsen, Gabriela Segal, Flavio Salazar-Onfray, Johanna Roa, Borbala Gesser, Rolf Kiessling, Aniruddha Choudhury, Mercedes N. López, Mónica Kurte, Ariadna Mendoza-Naranjo, Claudio A. Perez, Andrea Villablanca |
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Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Cellular differentiation
T-Lymphocytes Immunology Antigen presentation Biology Major histocompatibility complex T-Lymphocytes Regulatory Monocytes Immune tolerance Phagocytosis Transforming Growth Factor beta medicine Immune Tolerance Immunology and Allergy Humans Monocyte FOXP3 Cell Differentiation Hematology Dendritic Cells Interleukin-12 Cell biology Interleukin-10 medicine.anatomical_structure Phenotype Monocyte differentiation biology.protein Interleukin 12 Peptides Oligopeptides Signal Transduction |
Zdroj: | IMMUNOBIOLOGY Artículos CONICYT CONICYT Chile instacron:CONICYT López, M N, Pesce, B, Kurte, M, Pérez, C, Segal, G, Roa, J, Aguillón, J C, Mendoza-Naranjo, A, Gesser, B, Larsen, C, Villablanca, A, Choudhury, A, Kiessling, R & Salazar-Onfray, F 2011, ' A synthetic peptide homologous to IL-10 functional domain induces monocyte differentiation to TGF-β+ tolerogenic dendritic cells ', Immunobiology, vol. 216, no. 10, pp. 1117-1126 . https://doi.org/10.1016/j.imbio.2011.04.006 |
DOI: | 10.1016/j.imbio.2011.04.006 |
Popis: | We have previously demonstrated that IT9302, a nonameric peptide homologous to the C-terminal domain of human IL-10, mimics several effects of the cytokine including down-regulation of the antigen presentation machinery and increased sensitivity of tumor cells to NK-mediated lysis. In the present report, we have explored a potential therapeutic utility for IT9302 related to the ex vivo production of tolerogenic dendritic cells (DCs). Our results indicate that IT9302 impedes human monocyte response to differentiation factors and reduces antigen presentation and co-stimulatory capacity by DCs. Additionally, peptide-treated DCs show impaired capacity to stimulate T-cell proliferation and IFN-gamma production. IT9302 exerts its effect through mechanisms, in part, distinct from IL-10, involving STAT3 inactivation and NF-kappa B intracellular pathway. IT9302-treated DCs display increased expression of membrane-associated TGF-beta, linked to a more effective induction of foxp3+ regulatory T cells. These results illustrate for the first time that a short synthetic peptide can promote monocytes differentiation to tolerogenic DCs with therapeutic potential for the treatment of autoimmune and transplantation-related immunopathologic disease. (c) 2011 Elsevier GmbH. All rights reserved. |
Databáze: | OpenAIRE |
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