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2016 ; 149
(1
): 48-61
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Rel B-modified dendritic cells possess tolerogenic phenotype and functions on
lupus splenic lymphocytes in vitro
#MMPMID27278094
Wu H
; Lo Y
; Chan A
; Law KS
; Mok MY
Immunology
2016[Sep]; 149
(1
): 48-61
PMID27278094
show ga
Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized
by high morbidity and mortality and its treatment remains challenging. Dendritic
cells (DCs) have been shown to participate in the initiation and perpetuation of
lupus pathogenesis and the DCs that can induce tolerogenicity appear as potential
cell-based therapy in this condition. In this study, we examined the in vitro
tolerogenic properties of bone-marrow derived DCs (BMDCs) in the murine lupus
setting. We used lentiviral transduction of RelB-silencing short hairpin RNA to
modify the expression of RelB, a key transcription factor regulating DC
maturation, in BMDCs from MRL/MpJ mice. Tolerogenic properties of RelB-modified
DCs were compared with scrambled control (SC) -modified DCs. RelB expression was
found to be significantly reduced in RelB-modified DCs derived from MRL/MpJ mice,
wild-type of the same genetic background as MRL/lpr lupus-prone mice. These
MRL/MpJ RelB-modified DCs displayed semi-mature phenotype with expression of
lower levels of co-stimulatory molecules compared with SC-modified DCs.
RelB-modified DCs were found to be low producers of interleukin-12p70 (IL-12p70)
and could induce hyporesponsiveness of splenic T cells from MRL/MpJ and MRL/lpr
mice. Furthermore, they down-regulated interferon-? expression and induced
IL-10-producing T cells in MRL/MpJ splenocytes, and attenuated interferon-? and
IL-17 expression in MRL/lpr splenic CD4(+) lymphocytes. Splenocytes primed by
RelB-modified DCs demonstrated antigen-specific suppressive effects on allogeneic
splenocytes. In conclusion, RelB-silencing in DCs generates DCs of tolerogenic
properties with immunomodulatory function and appears as potential option of
cell-targeted therapy.