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Anti-dsDNA antibodies bind to TLR4 and activate NLRP3 inflammasome in lupus monocytes/macrophages

Overview of attention for article published in Journal of Translational Medicine, June 2016
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Title
Anti-dsDNA antibodies bind to TLR4 and activate NLRP3 inflammasome in lupus monocytes/macrophages
Published in
Journal of Translational Medicine, June 2016
DOI 10.1186/s12967-016-0911-z
Pubmed ID
Authors

Hui Zhang, Rong Fu, Chaohuan Guo, Yuefang Huang, Hongyue Wang, Shuang Wang, Jijun Zhao, Niansheng Yang

Abstract

NLRP3 inflammasome has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The activation of NLRP3 inflammasome results in the production of IL-1β and the subsequent inflammation. Anti-dsDNA antibodies (anti-dsDNA Abs) play critical roles in the development and progression of SLE. However, the mechanism of NLRP3 inflammasome activation in SLE is still not known. This study investigated the activation of NLRP3 inflammasome stimulated by anti-dsDNA Abs in monocytes/macrophages from SLE patients. Monocytes/macrophages from SLE patients or healthy controls were stimulated with anti-dsDNA Ab-positive serum or purified anti-dsDNA Abs. Activation of inflammasome was measured by flow cytometry or Western blot. Anti-dsDNA Abs isolated from active SLE patients were injected into female (NZB × NZW) F1 mice and the activation of NLRP3 inflammasome and the frequencies of Th17 and Treg were examined. The activity of caspase-1 was significantly increased in active SLE patients and was correlated with serum levels of anti-dsDNA Abs and disease activities. The concentrations of IL-1β and IL-17A were also significantly higher in SLE patients compared to healthy controls. Anti-dsDNA Ab-positive serum rather than healthy serum or RF (rheumatoid factor)-positive serum stimulated the activation of caspase-1 in monocytes. Anti-dsDNA Abs bound to TLR4 on macrophages and induced the production of ROS. Mitochondria-targeting antioxidant Mito-TEMPO, IκB kinase inhibitor peptide or TLR4 siRNA inhibited the activation of NLRP3 inflammasome and the secretion of IL-1β induced by anti-dsDNA Abs. Injection of anti-dsDNA Abs into (NZB × NZW) F1 mice resulted in increased caspase-1 activation and production of IL-1β and IL-17A. The Th17/Treg cell ratio also significantly increased following anti-dsDNA Ab injection. Anti-dsDNA Abs activated NLRP3 inflammasome in monocytes/macrophages from SLE patients by binding to TLR4 and inducing the production of mitochondrial ROS.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
China 1 3%
Unknown 39 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 20%
Student > Bachelor 7 18%
Researcher 7 18%
Student > Master 5 13%
Other 3 8%
Other 7 18%
Unknown 3 8%
Readers by discipline Count As %
Medicine and Dentistry 10 25%
Agricultural and Biological Sciences 8 20%
Immunology and Microbiology 7 18%
Biochemistry, Genetics and Molecular Biology 3 8%
Arts and Humanities 1 3%
Other 4 10%
Unknown 7 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 14 June 2016.
All research outputs
#6,383,197
of 11,220,852 outputs
Outputs from Journal of Translational Medicine
#994
of 2,179 outputs
Outputs of similar age
#127,875
of 277,793 outputs
Outputs of similar age from Journal of Translational Medicine
#50
of 114 outputs
Altmetric has tracked 11,220,852 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 2,179 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one is in the 46th percentile – i.e., 46% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 277,793 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 114 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.