Abstract:
: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.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
García-González PA,Schinnerling K,Sepúlveda-Gutiérrez A,Maggi J,Hoyos L,Morales RA,Mehdi AM,Nel HJ,Soto L,Pesce B,Molina MC,Cuchacovich M,Larrondo ML,Neira Ó,Catalán DF,Hilkens CM,Thomas R,Verdugo RA,Aguillón JCdoi
10.3389/fimmu.2016.00458subject
Has Abstractpub_date
2016-10-25 00:00:00pages
458issn
1664-3224journal_volume
7pub_type
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