PMID- 21742974
OWN - NLM
STAT- MEDLINE
DCOM- 20110929
LR  - 20171116
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 187
IP  - 4
DP  - 2011 Aug 15
TI  - Inhibition of microRNA let-7i depresses maturation and functional state of 
      dendritic cells in response to lipopolysaccharide stimulation via targeting 
      suppressor of cytokine signaling 1.
PG  - 1674-83
LID - 10.4049/jimmunol.1001937 [doi]
AB  - Dendritic cells (DCs) can initiate immune responses or confer immune tolerance 
      depending on functional status. LPS-induced DC maturation is defined by enhanced 
      surface expression of CD80 and CD86. MicroRNAs are critical for the regulation of 
      DC function and immunity, and the microRNA let-7i was upregulated during 
      LPS-induced DC maturation. Downregulation of let-7i significantly impeded DC 
      maturation as evidenced by reduced CD80 and CD86 expression. DCs stimulated by 
      LPS promoted T cell proliferation in coculture, whereas LPS-stimulated DCs with 
      downregulated let-7i were not effective at stimulating T cell proliferation but 
      promoted expansion of the regulatory T cell (Treg) population. There were two 
      subpopulations of LPS-stimulated DCs with downregulated let-7i, CD86(-) and 
      CD86(+), and it was the CD86(-) DCs that were more effective in inducing T cell 
      hyporesponsiveness and enhancing Treg numbers, indicating that this DC population 
      had tolerogenic properties. Furthermore, Tregs with upregulated IL-10 underscored 
      the tolerogenic effect of CD86(-) DCs. Suppressor of cytokine signaling 1 
      (SOCS1), a crucial mediator of DC maturation, was confirmed as a let-7i target 
      gene by luciferase construct assay. Suppression or overexpression of let-7i 
      caused reciprocal alterations in SOCS1 protein expression, but had no significant 
      effects on SOCS1 mRNA levels, indicating that let-7i regulated SOCS1 expression 
      by translational suppression. The modulation of SOCS1 protein by let-7i was 
      mainly restricted to CD86(-) DCs. Our study demonstrates that let-7i regulation 
      of SOCS1 is critical for LPS-induced DC maturation and immune function. Dynamic 
      regulation of let-7i may fine-tune immune responses by inducing Ag-specific 
      immune tolerance.
FAU - Zhang, Maomao
AU  - Zhang M
AD  - Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and 
      Treatment, Harbin Medical University, Harbin, Heilongjiang Province 150081, 
      China.
FAU - Liu, Fang
AU  - Liu F
FAU - Jia, Haibo
AU  - Jia H
FAU - Zhang, Qi
AU  - Zhang Q
FAU - Yin, Li
AU  - Yin L
FAU - Liu, Wei
AU  - Liu W
FAU - Li, Hulun
AU  - Li H
FAU - Yu, Bo
AU  - Yu B
FAU - Wu, Jian
AU  - Wu J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110708
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (Cd86 protein, rat)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MicroRNAs)
RN  - 0 (Socs1 protein, rat)
RN  - 0 (Suppressor of Cytokine Signaling 1 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
SB  - IM
MH  - Animals
MH  - B7-1 Antigen/genetics/immunology
MH  - B7-2 Antigen/genetics/immunology
MH  - Cell Proliferation
MH  - Dendritic Cells/*immunology/metabolism
MH  - Gene Expression Regulation/genetics/immunology
MH  - Lipopolysaccharides/*pharmacology
MH  - MicroRNAs/genetics/*immunology/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Suppressor of Cytokine Signaling 1 Protein
MH  - Suppressor of Cytokine Signaling Proteins/genetics/*immunology
MH  - T-Lymphocytes/immunology
EDAT- 2011/07/12 06:00
MHDA- 2011/10/01 06:00
CRDT- 2011/07/12 06:00
PHST- 2011/07/12 06:00 [entrez]
PHST- 2011/07/12 06:00 [pubmed]
PHST- 2011/10/01 06:00 [medline]
AID - jimmunol.1001937 [pii]
AID - 10.4049/jimmunol.1001937 [doi]
PST - ppublish
SO  - J Immunol. 2011 Aug 15;187(4):1674-83. doi: 10.4049/jimmunol.1001937. Epub 2011 
      Jul 8.