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Overexpression of microRNA-155 increases IL-21 mediated STAT3 signaling and IL-21 production in systemic lupus erythematosus

Overview of attention for article published in Arthritis Research & Therapy, June 2015
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Title
Overexpression of microRNA-155 increases IL-21 mediated STAT3 signaling and IL-21 production in systemic lupus erythematosus
Published in
Arthritis Research & Therapy, June 2015
DOI 10.1186/s13075-015-0660-z
Pubmed ID
Authors

Tue Kruse Rasmussen, Thomas Andersen, Rasmus Otkjær Bak, Gloria Yiu, Christian Møller Sørensen, Kristian Stengaard-Pedersen, Jacob Giehm Mikkelsen, Paul Joseph Utz, Christian Kanstrup Holm, Bent Deleuran

Abstract

Interleukin (IL-)21 is a key cytokine in autoimmune diseases such as systemic lupus erythematosus (SLE) by its regulation of autoantibody production and inflammatory responses. The objective of this study is to investigate the signaling capacity of IL-21 in T and B cells and assess its possible regulation by microRNA (miR)-155 and its target gene suppressor of cytokine signaling 1 (SOCS1) in SLE. The signaling capacity of IL-21 was quantified by stimulating peripheral blood monocuclear cells (PBMCs) with IL-21 and measuring phosphorylation of STAT3 (pSTAT3) in CD4+ T cells, B cells, and NK cells. Induction of miR-155 by IL-21 was investigated by stimulating purified CD4+ T cells with IL-21 and measuring miR-155 expression levels. The functional role of miR-155 was assessed by overexpressing miR-155 in PBMCs from SLE patients and healthy controls (HCs) and measuring its effects on STAT3 and IL-21 production in CD4+ and CD8+ T cells. Induction of pSTAT3 in CD4+ T cells in response to IL-21 was significantly decreased in SLE patients compared to HCs (p < 0.0001). Further, expression levels of miR-155 were significantly decreased and SOCS1 correspondingly increased in CD4+ T cells from SLE patients. Finally, overexpression of miR-155 in CD4+ T cells increased STAT3 phosphorylation in response to IL-21 treatment (p < 0.01) and differentially increased IL-21 production in SLE patients compared to HCs (p < 0.01). We demonstrate that SLE patients have reduced IL-21 signaling capacity, decreased miR-155 levels, and increased SOCS1 levels compared to HCs. The reduced IL-21 signaling in SLE could be rescued by overexpression of miR-155, suggesting an important role for miR-155 in the reduced IL-21 signaling observed in SLE.

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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 %
United Kingdom 1 3%
Unknown 39 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 18%
Student > Master 5 13%
Researcher 4 10%
Student > Bachelor 4 10%
Other 3 8%
Other 6 15%
Unknown 11 28%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 20%
Medicine and Dentistry 7 18%
Biochemistry, Genetics and Molecular Biology 5 13%
Immunology and Microbiology 4 10%
Computer Science 1 3%
Other 3 8%
Unknown 12 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 10 June 2015.
All research outputs
#9,566,798
of 12,451,992 outputs
Outputs from Arthritis Research & Therapy
#1,651
of 1,983 outputs
Outputs of similar age
#146,909
of 231,593 outputs
Outputs of similar age from Arthritis Research & Therapy
#19
of 30 outputs
Altmetric has tracked 12,451,992 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,983 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one is in the 16th percentile – i.e., 16% 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 231,593 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.