Treatment with dexamethasone and monophosphoryl lipid a removes disease-associated transcriptional signatures in monocyte-derived dendritic cells from rheumatoid arthritis patients and confers tolerogenic features
Author
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García González, Paulina
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Schinnerling, Katina
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Sepúlveda Gutiérrez, Alejandro
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Maggi, Jaxaira
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Hoyos, Lorena
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Morales, Rodrigo
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Mehdi, Ahmed
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Nel, Hendrik
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Soto Sáez, Lilian
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Pesce Reyes, Bárbara
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Molina Sampayo, María Carmen
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Cuchacovich Turteltaub, Miguel
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Larrondo Lillo, Milton
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Neira, Oscar
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Catalán Martina, Diego
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Hilkens, Catharien M.
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Thomas, Ranjeny
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Verdugo Salgado, Ricardo
Author
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Aguillón Gutiérrez, Juan Carlos
Admission date
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2017-11-10T12:52:39Z
Available date
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2017-11-10T12:52:39Z
Publication date
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2016-10-25
Cita de ítem
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Front. Immunol. 7:458.
es_ES
Identifier
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10.3389/fimmu.2016.00458
Identifier
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https://repositorio.uchile.cl/handle/2250/145580
Abstract
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Tolerogenic dendritic cells (TolDCs) are promising tools for therapy of autoimmune diseases, such as rheumatoid arthritis (RA). Here, we characterize monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated with monophosphoryl lipid A (MPLA), referred to as MPLA-tDCs, in terms of gene expression, phenotype, cytokine profile, migratory properties, and T cell-stimulatory capacity in order to explore their suitability for cellular therapy. MPLA-tDCs derived from RA patients displayed an anti-inflammatory profile with reduced expression of co-stimulatory molecules and high IL-10/IL-12 ratio, but were capable of migrating toward the lymphoid chemokines CXCL12 and CCL19. These MPLA-tDCs induced hyporesponsiveness of autologous CD4+ T cells specific for synovial antigens in vitro. Global transcriptome analysis confirmed a unique transcriptional profile of MPLA-tDCs and revealed that RA-associated genes, which were upregulated in untreated DCs from RA patients, returned to expression levels of healthy donor-derived DCs after treatment with dexamethasone and MPLA. Thus, monocyte-derived DCs from RA patients have the capacity to develop tolerogenic features at transcriptional as well as at translational level, when modulated with dexamethasone and MPLA, overcoming disease-related effects. Furthermore, the ability of MPLA-tDCs to impair T cell responses to synovial antigens validates their potential as cellular treatment for RA.
es_ES
Patrocinador
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This work was supported by Fondecyt-Chile 1140553, and Millennium Institute on Immunology and Immunotherapy P09-016-F.
Treatment with dexamethasone and monophosphoryl lipid a removes disease-associated transcriptional signatures in monocyte-derived dendritic cells from rheumatoid arthritis patients and confers tolerogenic features