PMID- 23383203
OWN - NLM
STAT- MEDLINE
DCOM- 20130717
LR  - 20220316
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 1
DP  - 2013
TI  - Novel mechanism of inhibition of dendritic cells maturation by mesenchymal stem 
      cells via interleukin-10 and the JAK1/STAT3 signaling pathway.
PG  - e55487
LID - 10.1371/journal.pone.0055487 [doi]
LID - e55487
AB  - Mesenchymal stem cells (MSCs) can suppress dendritic cells (DCs) maturation and 
      function, mediated by soluble factors, such as indoleamine 2,3-dioxygenase (IDO), 
      prostaglandin E(2) (PGE(2)), and nitric oxide (NO). Interleukin-10 (IL-10) is a 
      common immunosuppressive cytokine, and the downstream signaling of the JAK-STAT 
      pathway has been shown to be involved with DCs differentiation and maturation in 
      the context of cancer. Whether IL-10 and/or the JAK-STAT pathway play a role in 
      the inhibitory effect of MSCs on DCs maturation remains controversial. In our 
      study, we cultured MSCs and DCs derived from rat bone marrow under different 
      culturing conditions. Using Transwell plates, we detected by ELISA that the level 
      of IL-10 significantly increased in the supernatants of MSC-DC co-cultures at 48 
      hours. The cell immunofluorescence assay suggested that the MSCs secreted more 
      IL-10 than the DCs in the co-cultures. Adding exogenous IL-10 to the DCs 
      monoculture or MSC-DC co-cultures stimulated IL-10 and led to a decrease in 
      IL-12, and lower expression of the DCs surface markers CD80, CD86, OX62, MHC-II 
      and CD11b/c. Supplementing the culture with an IL-10 neutralizing antibody 
      (IL-10NA) showed precisely the opposite effect of adding IL-10. Moreover, we 
      demonstrated that the JAK-STAT signaling pathway is involved in inhibiting DCs 
      maturation. Both JAK1 and STAT3 expression and IL-10 secretion decreased markedly 
      after adding a JAK inhibitor (AG490) to the co-culture plate. We propose that 
      there is an IL-10 positive feedback loop, which may explain our observations of 
      elevated IL-10 and enhanced JAK1 and STAT3 expression. Overall, we demonstrated 
      that MSCs inhibit the maturation of DCs through the stimulation of IL-10 
      secretion, and by activating the JAK1 and STAT3 signaling pathway.
FAU - Liu, Wen-hua
AU  - Liu WH
AD  - Intensive Care Unit (ICU) Department, Second Affiliated Hospital of Harbin 
      Medical University, Harbin, Province Heilongjiang, China.
FAU - Liu, Jing-jin
AU  - Liu JJ
FAU - Wu, Jian
AU  - Wu J
FAU - Zhang, Lu-lu
AU  - Zhang LL
FAU - Liu, Fang
AU  - Liu F
FAU - Yin, Li
AU  - Yin L
FAU - Zhang, Mao-mao
AU  - Zhang MM
FAU - Yu, Bo
AU  - Yu B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20130130
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Lipopolysaccharides)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Tyrphostins)
RN  - 0 (alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - EC 2.7.10.2 (Janus Kinase 1)
SB  - IM
RIN - PLoS One. 2018 Mar 14;13(3):e0194455. PMID: 29538460
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/cytology/drug effects/immunology/*metabolism
MH  - Immunophenotyping
MH  - Interleukin-10/*metabolism/pharmacology
MH  - Interleukin-12/metabolism
MH  - Janus Kinase 1/*metabolism
MH  - Lipopolysaccharides/immunology
MH  - Male
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - STAT3 Transcription Factor/*metabolism
MH  - *Signal Transduction
MH  - Tyrphostins/pharmacology
PMC - PMC3559548
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/02/06 06:00
MHDA- 2013/07/19 06:00
PMCR- 2013/01/30
CRDT- 2013/02/06 06:00
PHST- 2012/08/14 00:00 [received]
PHST- 2012/12/27 00:00 [accepted]
PHST- 2013/02/06 06:00 [entrez]
PHST- 2013/02/06 06:00 [pubmed]
PHST- 2013/07/19 06:00 [medline]
PHST- 2013/01/30 00:00 [pmc-release]
AID - PONE-D-12-24603 [pii]
AID - 10.1371/journal.pone.0055487 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(1):e55487. doi: 10.1371/journal.pone.0055487. Epub 2013 Jan 30.