↓ Skip to main content

Myeloid C/EBPβ deficiency reshapes microglial gene expression and is protective in experimental autoimmune encephalomyelitis

Overview of attention for article published in Journal of Neuroinflammation, March 2017
Altmetric Badge

Mentioned by

twitter
1 X user

Citations

dimensions_citation
20 Dimensions

Readers on

mendeley
65 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Myeloid C/EBPβ deficiency reshapes microglial gene expression and is protective in experimental autoimmune encephalomyelitis
Published in
Journal of Neuroinflammation, March 2017
DOI 10.1186/s12974-017-0834-5
Pubmed ID
Authors

Marta Pulido-Salgado, Jose M. Vidal-Taboada, Gerardo Garcia Diaz-Barriga, Joan Serratosa, Tony Valente, Paola Castillo, Jonathan Matalonga, Marco Straccia, Josep M. Canals, Annabel Valledor, Carme Solà, Josep Saura

Abstract

CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage, but the involvement in this neuroprotective effect of the various C/EBPβ-expressing cell types is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture, we hypothesized that specific C/EBPβ deficiency in microglia could be neuroprotective in vivo. In this study, we have tested this hypothesis by generating mice with myeloid C/EBPβ deficiency. Mice with myeloid C/EBPβ deficiency were generated by crossing LysMCre and C/EBPβ(fl/fl) mice. Primary microglial cultures from C/EBPβ(fl/fl) and LysMCre-C/EBPβ(fl/fl) mice were treated with lipopolysaccharide ± interferon γ (IFNγ) for 6 h, and gene expression was analyzed by RNA sequencing. Gene expression and C/EBPβ deletion were analyzed in vivo in microglia isolated from the brains of C/EBPβ(fl/fl) and LysMCre-C/EBPβ(fl/fl) mice treated systemically with lipolysaccharide or vehicle. Mice of LysMCre-C/EBPβ(fl/fl) or control genotypes were subjected to experimental autoimmune encephalitis and analyzed for clinical signs for 52 days. One- or two-way ANOVA or Kruskal-Wallis with their appropriate post hoc tests were used. LysMCre-C/EBPβ(fl/fl) mice showed an efficiency of C/EBPβ deletion in microglia of 100 and 90% in vitro and in vivo, respectively. These mice were devoid of female infertility, perinatal mortality and reduced lifespan that are associated to full C/EBPβ deficiency. Transcriptomic analysis of C/EBPβ-deficient primary microglia revealed C/EBPβ-dependent expression of 1068 genes, significantly enriched in inflammatory and innate immune responses GO terms. In vivo, microglial expression of the pro-inflammatory genes Cybb, Ptges, Il23a, Tnf and Csf3 induced by systemic lipopolysaccharide injection was also blunted by C/EBPβ deletion. CNS expression of C/EBPβ was upregulated in experimental autoimmune encephalitis and in multiple sclerosis samples. Finally, LysMCre-C/EBPβ(fl/fl) mice showed robust attenuation of clinical signs in experimental autoimmune encephalitis. This study provides new data that support a central role for C/EBPβ in the biology of activated microglia, and it offers proof of concept for the therapeutic potential of microglial C/EBPβ inhibition in multiple sclerosis.

X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 65 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 65 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 20%
Researcher 9 14%
Student > Master 7 11%
Student > Bachelor 6 9%
Student > Postgraduate 6 9%
Other 17 26%
Unknown 7 11%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 23%
Medicine and Dentistry 11 17%
Neuroscience 10 15%
Agricultural and Biological Sciences 10 15%
Computer Science 2 3%
Other 8 12%
Unknown 9 14%
Attention Score in Context

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 28 March 2017.
All research outputs
#20,411,380
of 22,961,203 outputs
Outputs from Journal of Neuroinflammation
#2,318
of 2,649 outputs
Outputs of similar age
#268,995
of 308,429 outputs
Outputs of similar age from Journal of Neuroinflammation
#44
of 55 outputs
Altmetric has tracked 22,961,203 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,649 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 1st percentile – i.e., 1% 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 308,429 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 55 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.