PMID- 23943615
OWN - NLM
STAT- MEDLINE
DCOM- 20131224
LR  - 20211203
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 39
DP  - 2013 Sep 27
TI  - Fas signal promotes the immunosuppressive function of regulatory dendritic cells 
      via the ERK/beta-catenin pathway.
PG  - 27825-35
LID - 10.1074/jbc.M112.425751 [doi]
AB  - Dendritic cells (DCs) play important roles in the initiation of immune response 
      and also in the maintenance of immune tolerance. Now, many kinds of regulatory 
      DCs with different phenotypes have been identified to suppress immune response 
      and contribute to the control of autoimmune diseases. However, the mechanisms by 
      which regulatory DCs can be regulated to exert the immunosuppressive function in 
      the immune microenvironment remain to be fully investigated. In addition, how T 
      cells, once activated, can feedback affect the function of regulatory DCs during 
      immune response needs to be further identified. We previously identified a unique 
      subset of CD11b(hi)Ia(low) regulatory DCs, differentiated from mature DCs or 
      hematopoietic stem cells under a stromal microenvironment in spleen and liver, 
      which can negatively regulate immune response in a feedback way. Here, we show 
      that CD11b(hi)Ia(low) regulatory DCs expressed high level of Fas, and endothelial 
      stromal cell-derived TGF-beta could induce high expression of Fas on regulatory DCs 
      via ERK activation. Fas ligation could promote regulatory DCs to inhibit CD4(+) T 
      cell proliferation more significantly. Furthermore, Fas ligation preferentially 
      induced regulatory DCs to produce IL-10 and IP-10 via ERK-mediated inactivation 
      of GSK-3 and subsequent up-regulation of beta-catenin. Interestingly, activated T 
      cells could promote regulatory DCs to secrete more IL-10 and IP-10 partially 
      through FasL. Therefore, our results demonstrate that Fas signal, at least from 
      the activated T cells, can promote the immunosuppressive function of 
      Fas-expressing regulatory DCs, providing a new manner for the regulatory DCs to 
      regulate adaptive immunity.
FAU - Qian, Cheng
AU  - Qian C
AD  - From the National Key Laboratory of Medical Immunology and Institute of 
      Immunology, Second Military Medical University, Shanghai 200433, China.
FAU - Qian, Li
AU  - Qian L
FAU - Yu, Yizhi
AU  - Yu Y
FAU - An, Huazhang
AU  - An H
FAU - Guo, Zhenhong
AU  - Guo Z
FAU - Han, Yanmei
AU  - Han Y
FAU - Chen, Yongjian
AU  - Chen Y
FAU - Bai, Yi
AU  - Bai Y
FAU - Wang, Qingqing
AU  - Wang Q
FAU - Cao, Xuetao
AU  - Cao X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130813
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Fas protein, mouse)
RN  - 0 (beta Catenin)
RN  - 0 (fas Receptor)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
EIN - J Biol Chem. 2014 Feb 28;289(9):5534-5
MH  - Active Transport, Cell Nucleus
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - CD4-Positive T-Lymphocytes/cytology
MH  - Chemokine CXCL10/metabolism
MH  - Dendritic Cells/*cytology
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Homeostasis
MH  - Immune System
MH  - Immunosuppression Therapy
MH  - Interleukin-10/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Signal Transduction
MH  - beta Catenin/*metabolism
MH  - fas Receptor/*metabolism
PMC - PMC3784698
OTO - NOTNLM
OT  - Catenin
OT  - Dendritic Cells
OT  - ERK
OT  - Fas
OT  - Tolerance
EDAT- 2013/08/15 06:00
MHDA- 2013/12/25 06:00
PMCR- 2014/09/27
CRDT- 2013/08/15 06:00
PHST- 2013/08/15 06:00 [entrez]
PHST- 2013/08/15 06:00 [pubmed]
PHST- 2013/12/25 06:00 [medline]
PHST- 2014/09/27 00:00 [pmc-release]
AID - S0021-9258(20)48908-2 [pii]
AID - M112.425751 [pii]
AID - 10.1074/jbc.M112.425751 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 Sep 27;288(39):27825-35. doi: 10.1074/jbc.M112.425751. Epub 
      2013 Aug 13.