PMID- 25825436
OWN - NLM
STAT- MEDLINE
DCOM- 20150630
LR  - 20181202
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 194
IP  - 9
DP  - 2015 May 1
TI  - Sca-1+Lin-CD117- mesenchymal stem/stromal cells induce the generation of novel 
      IRF8-controlled regulatory dendritic cells through Notch-RBP-J signaling.
PG  - 4298-308
LID - 10.4049/jimmunol.1402641 [doi]
AB  - Mesenchymal stem/stromal cells (MSCs) can influence the destiny of hematopoietic 
      stem/progenitor cells (HSCs) and exert broadly immunomodulatory effects on immune 
      cells. However, how MSCs regulate the differentiation of regulatory dendritic 
      cells (regDCs) from HSCs remains incompletely understood. In this study, we show 
      that mouse bone marrow-derived Sca-1(+)Lin(-)CD117(-) MSCs can drive HSCs to 
      differentiate into a novel IFN regulatory factor (IRF)8-controlled regDC 
      population (Sca(+) BM-MSC-driven DC [sBM-DCs]) when cocultured without exogenous 
      cytokines. The Notch pathway plays a critical role in the generation of the 
      sBM-DCs by controlling IRF8 expression in an RBP-J-dependent way. We observed a 
      high level of H3K27me3 methylation and a low level of H3K4me3 methylation at the 
      Irf8 promoter during sBM-DC induction. Importantly, infusion of sBM-DCs could 
      alleviate colitis in mice with inflammatory bowel disease by inhibiting 
      lymphocyte proliferation and increasing the numbers of CD4(+)CD25(+) regulatory T 
      cells. Thus, these data infer a possible mechanism for the development of regDCs 
      and further support the role of MSCs in treating immune disorders.
CI  - Copyright (c) 2015 by The American Association of Immunologists, Inc.
FAU - Liu, Xingxia
AU  - Liu X
AD  - Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, 
      Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union 
      Medical College, Peking Union Medical College Hospital, Chinese Academy of 
      Medical Sciences, Beijing 100005, People's Republic of China;
FAU - Ren, Shaoda
AU  - Ren S
AD  - Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, 
      Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union 
      Medical College, Peking Union Medical College Hospital, Chinese Academy of 
      Medical Sciences, Beijing 100005, People's Republic of China;
FAU - Ge, Chaozhuo
AU  - Ge C
AD  - Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, 
      Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union 
      Medical College, Peking Union Medical College Hospital, Chinese Academy of 
      Medical Sciences, Beijing 100005, People's Republic of China;
FAU - Cheng, Kai
AU  - Cheng K
AD  - Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, 
      Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union 
      Medical College, Peking Union Medical College Hospital, Chinese Academy of 
      Medical Sciences, Beijing 100005, People's Republic of China;
FAU - Zenke, Martin
AU  - Zenke M
AD  - Department of Cell Biology, Institute for Biomedical Engineering, 
      Rhenish-Westphalian Technical University, Aachen University Medical School, 52074 
      Aachen, Germany;
FAU - Keating, Armand
AU  - Keating A
AD  - Cell Therapy Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, 
      Canada; and Institute of Biomaterials and Biomedical Engineering, University of 
      Toronto, Toronto, Ontario M5G 2M9, Canada.
FAU - Zhao, Robert C H
AU  - Zhao RC
AD  - Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, 
      Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union 
      Medical College, Peking Union Medical College Hospital, Chinese Academy of 
      Medical Sciences, Beijing 100005, People's Republic of China; 
      zhaochunhua@vip.163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150330
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, Ly)
RN  - 0 (Cytokines)
RN  - 0 (Histones)
RN  - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (Ly6a protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Rbpj protein, mouse)
RN  - 0 (Receptors, Notch)
RN  - 0 (interferon regulatory factor-8)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Animals
MH  - Antigens, Ly/metabolism
MH  - Cell Differentiation
MH  - Cytokines/metabolism
MH  - Dendritic Cells/cytology/*immunology/*metabolism
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - Histones/metabolism
MH  - Immunoglobulin J Recombination Signal Sequence-Binding Protein/*metabolism
MH  - Immunomodulation
MH  - Inflammation Mediators/metabolism
MH  - Inflammatory Bowel Diseases/immunology/metabolism/pathology
MH  - Interferon Regulatory Factors/genetics/*metabolism
MH  - Membrane Proteins/metabolism
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Models, Biological
MH  - Phenotype
MH  - Proto-Oncogene Proteins c-kit/metabolism
MH  - Receptors, Notch/*metabolism
MH  - *Signal Transduction
EDAT- 2015/04/01 06:00
MHDA- 2015/07/01 06:00
CRDT- 2015/04/01 06:00
PHST- 2014/10/21 00:00 [received]
PHST- 2015/02/27 00:00 [accepted]
PHST- 2015/04/01 06:00 [entrez]
PHST- 2015/04/01 06:00 [pubmed]
PHST- 2015/07/01 06:00 [medline]
AID - jimmunol.1402641 [pii]
AID - 10.4049/jimmunol.1402641 [doi]
PST - ppublish
SO  - J Immunol. 2015 May 1;194(9):4298-308. doi: 10.4049/jimmunol.1402641. Epub 2015 
      Mar 30.