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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

Lookup NU author(s): Professor Catharien Hilkens

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

olerogenic 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.

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Author(s): 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, Aguilón JC

Publication type: Article

Publication status: Published

Journal: Frontiers in Immunology

Year: 2016

Volume: 7

Print publication date: 25/10/2016

Online publication date: 25/10/2016

Acceptance date: 12/10/2016

Date deposited: 15/11/2016

ISSN (electronic): 1664-3224

Publisher: Frontiers Research Foundation

URL: http://dx.doi.org/10.3389/fimmu.2016.00458

DOI: 10.3389/fimmu.2016.00458

PubMed id: 27826300

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