PMID- 27278094
OWN - NLM
STAT- MEDLINE
DCOM- 20170512
LR  - 20181113
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 149
IP  - 1
DP  - 2016 Sep
TI  - Rel B-modified dendritic cells possess tolerogenic phenotype and functions on 
      lupus splenic lymphocytes in vitro.
PG  - 48-61
LID - 10.1111/imm.12628 [doi]
AB  - 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-gamma expression and induced 
      IL-10-producing T cells in MRL/MpJ splenocytes, and attenuated interferon-gamma 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.
CI  - (c) 2016 The Authors. Immunology Published by John Wiley & Sons Ltd.
FAU - Wu, Haijing
AU  - Wu H
AD  - Division of Rheumatology & Clinical Immunology, Department of Medicine, The 
      University of Hong Kong, Hong Kong.
FAU - Lo, Yi
AU  - Lo Y
AD  - Division of Rheumatology & Clinical Immunology, Department of Medicine, The 
      University of Hong Kong, Hong Kong.
FAU - Chan, Albert
AU  - Chan A
AD  - Division of Rheumatology & Clinical Immunology, Department of Medicine, The 
      University of Hong Kong, Hong Kong.
FAU - Law, Ka Sin
AU  - Law KS
AD  - Division of Rheumatology & Clinical Immunology, Department of Medicine, The 
      University of Hong Kong, Hong Kong.
FAU - Mok, Mo Yin
AU  - Mok MY
AD  - Division of Rheumatology & Clinical Immunology, Department of Medicine, The 
      University of Hong Kong, Hong Kong.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Interleukin-17)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Relb protein, mouse)
RN  - 130068-27-8 (Interleukin-10)
RN  - 147337-75-5 (Transcription Factor RelB)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cell Differentiation
MH  - Cell Line
MH  - Dendritic Cells/*immunology
MH  - Humans
MH  - Immune Tolerance
MH  - Immunotherapy, Adoptive/*methods
MH  - Interleukin-10/metabolism
MH  - Interleukin-12/metabolism
MH  - Interleukin-17/metabolism
MH  - Lupus Erythematosus, Systemic/*immunology
MH  - Mice
MH  - Mice, Inbred MRL lpr
MH  - RNA, Small Interfering/genetics
MH  - Spleen/*pathology
MH  - Transcription Factor RelB/genetics/*metabolism
PMC - PMC4981611
OTO - NOTNLM
OT  - dendritic cells
OT  - immune tolerance
OT  - immunotherapy
OT  - systemic lupus erythematosus
OT  - transcription factor
EDAT- 2016/06/10 06:00
MHDA- 2017/05/13 06:00
PMCR- 2017/09/01
CRDT- 2016/06/10 06:00
PHST- 2015/09/18 00:00 [received]
PHST- 2016/04/18 00:00 [revised]
PHST- 2016/05/28 00:00 [accepted]
PHST- 2016/06/10 06:00 [entrez]
PHST- 2016/06/10 06:00 [pubmed]
PHST- 2017/05/13 06:00 [medline]
PHST- 2017/09/01 00:00 [pmc-release]
AID - IMM12628 [pii]
AID - 10.1111/imm.12628 [doi]
PST - ppublish
SO  - Immunology. 2016 Sep;149(1):48-61. doi: 10.1111/imm.12628.