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NFκB signaling drives pro-granulocytic astroglial responses to neuromyelitis optica patient IgG

Overview of attention for article published in Journal of Neuroinflammation, September 2015
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2 tweeters

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22 Dimensions

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40 Mendeley
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Title
NFκB signaling drives pro-granulocytic astroglial responses to neuromyelitis optica patient IgG
Published in
Journal of Neuroinflammation, September 2015
DOI 10.1186/s12974-015-0403-8
Pubmed ID
Authors

Margaret E. Walker-Caulfield, Yong Guo, Renee K. Johnson, Christina B. McCarthy, Patrick D. Fitz-Gibbon, Claudia F. Lucchinetti, Charles L. Howe

Abstract

Astrocytes expressing the aquaporin-4 water channel are a primary target of pathogenic, disease-specific immunoglobulins (IgG) found in patients with neuromyelitis optica (NMO). Immunopathological analyses of active NMO lesions highlight a unique inflammatory phenotype marked by infiltration of granulocytes. Previous studies characterized this granulocytic infiltrate as a response to vasculocentric complement activation and localized tissue destruction. In contrast, we observe that granulocytic infiltration in NMO lesions occurs independently of complement-mediated tissue destruction or active demyelination. These immunopathological findings led to the hypothesis that NMO IgG stimulates astrocyte signaling that is responsible for granulocytic recruitment in NMO. Histopathology was performed on archival formalin-fixed paraffin-embedded autopsy-derived CNS tissue from 23 patients clinically and pathologically diagnosed with NMO or NMO spectrum disorder. Primary murine astroglial cultures were stimulated with IgG isolated from NMO patients or control IgG from healthy donors. Transcriptional responses were assessed by microarray, and translational responses were measured by ELISA. Signaling through the NFκB pathway was measured by western blotting and immunostaining. Stimulation of primary murine astroglial cultures with NMO IgG elicited a reactive and inflammatory transcriptional response that involved signaling through the canonical NFκB pathway. This signaling resulted in the release of pro-granulocytic chemokines and was inhibited by the clinically relevant proteasome inhibitors bortezomib and PR-957. We propose that the astrocytic NFκB-dependent inflammatory response to stimulation by NMO IgG represents one of the earliest events in NMO pathogenesis, providing a target for therapeutic intervention upstream of irreversible cell death and tissue damage.

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 %
Unknown 40 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 18%
Student > Ph. D. Student 6 15%
Student > Master 4 10%
Student > Bachelor 4 10%
Professor 3 8%
Other 11 28%
Unknown 5 13%
Readers by discipline Count As %
Neuroscience 9 23%
Medicine and Dentistry 6 15%
Agricultural and Biological Sciences 5 13%
Immunology and Microbiology 2 5%
Psychology 2 5%
Other 7 18%
Unknown 9 23%

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 23 June 2016.
All research outputs
#16,744,369
of 20,792,815 outputs
Outputs from Journal of Neuroinflammation
#1,876
of 2,417 outputs
Outputs of similar age
#187,257
of 264,360 outputs
Outputs of similar age from Journal of Neuroinflammation
#5
of 7 outputs
Altmetric has tracked 20,792,815 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,417 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one is in the 13th percentile – i.e., 13% 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 264,360 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 7 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.