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2016 ; 7
(ä): 458
Nephropedia Template TP
gab.com Text
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English Wikipedia
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
#MMPMID27826300
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 JC
Front Immunol
2016[]; 7
(ä): 458
PMID27826300
show ga
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.