Fang Liu, Chunxi Liu, Xiaoyu Hu, Yingli Shang, Li Wu
Abstract
Plasmacytoid dendritic cells (pDCs) are the major producers of type I and type III interferons (IFNs) that play essential roles in host antiviral immunity. MicroRNAs (miRs) are small, noncoding RNAs that can modulate many immune processes. Although molecular regulation of type I IFN production by pDCs has been studied extensively, the regulation of type III IFN production has not been studied thoroughly, particularly at posttranscriptional level. We show here that miR-21 is an essential positive regulator for the production of both IFN-α and IFN-λ by pDCs and for promoting host defense against viral infection. miR-21 was markedly upregulated in toll-like receptor (TLR)-activated pDCs and was crucial for TLR7/9 ligand- or herpesvirus-induced production of IFN-α and IFN-λ by pDCs. miR-21-deficient pDCs produced significantly lower levels of IFN-α and IFN-λ on activation than those by wild-type pDCs. Impaired antiviral immune responses were also observed in miR-21-deficient mice. Mechanistically, we identified phosphatase and tensin homolog (PTEN) as the major target of miR-21 in pDCs, and miR-21 deficiency resulted in increased expression of PTEN that suppressed TLR-mediated activation of PI3K-Akt-mTOR signaling in pDCs. Hence, our findings provide evidence that miR-21 positively regulates both IFN-α and IFN-λ production and identify an important role for miR-21 in regulating the function of pDCs and in host antiviral immunity.
Pharmacology, Toxicology and Pharmaceutical Science
1
5%
Agricultural and Biological Sciences
1
5%
Other
1
5%
Unknown
3
16%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 September 2017.
All research outputs
#15,104,505
of 25,870,940 outputs
Outputs from Frontiers in immunology
#13,272
of 32,522 outputs
Outputs of similar age
#165,451
of 330,068 outputs
Outputs of similar age from Frontiers in immunology
#226
of 447 outputs
Altmetric has tracked 25,870,940 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 32,522 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.5. This one has gotten more attention than average, scoring higher than 58% of its peers.
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We're also able to compare this research output to 447 others from the same source and published within six weeks on either side of this one. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.
