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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Sex-Specific Gene-by-Vitamin D Interactions Regulate Susceptibility to Central Nervous System Autoimmunity
|
|---|---|
| Published in |
Frontiers in immunology, July 2018
|
| DOI | 10.3389/fimmu.2018.01622 |
| Pubmed ID | |
| Authors |
Dimitry N. Krementsov, Loredana Asarian, Qian Fang, Mahalia M. McGill, Cory Teuscher |
| Abstract |
Vitamin D3 (VitD) insufficiency is postulated to represent a major modifiable risk factor for multiple sclerosis (MS). While low VitD levels strongly correlate with higher MS risk in white populations, this is not the case for other ethnic groups, suggesting the existence of a genetic component. Moreover, VitD supplementation studies in MS so far have not shown a consistent benefit. We sought to determine whether direct manipulation of VitD levels modulates central nervous system autoimmune disease in a sex-by-genotype-dependent manner. To this end, we used a dietary model of VitD modulation, together with the autoimmune animal model of MS, experimental autoimmune encephalomyelitis (EAE). To assess the impact of genotype-by-VitD interactions on EAE susceptibility, we utilized a chromosome substitution (consomic) mouse model that incorporates the genetic diversity of wild-derived PWD/PhJ mice. High VitD was protective in EAE in female, but not male C57BL/6J (B6) mice, and had no effect in EAE-resistant PWD/PhJ (PWD) mice. EAE protection was accompanied by sex- and genotype-specific suppression of proinflammatory transcriptional programs in CD4 T effector cells, but not CD4 regulatory T cells. Decreased expression of proinflammatory genes was observed with high VitD in female CD4 T effector cells, specifically implicating a key role of MHC class II genes, interferon gamma, and Th1 cell-mediated neuroinflammation. In consomic strains, effects of VitD on EAE were also sex- and genotype dependent, whereby high VitD: (1) was protective, (2) had no effect, and (3) unexpectedly had disease-exacerbating effects. Systemic levels of 25(OH)D differed across consomic strains, with higher levels associated with EAE protection only in females. Analysis of expression of key known VitD metabolism genes between B6 and PWD mice revealed that their expression is genetically determined and sex specific and implicated Cyp27b1 and Vdr as candidate genes responsible for differential EAE responses to VitD modulation. Taken together, our results support the observation that the association between VitD status and MS susceptibility is genotype dependent and suggest that the outcome of VitD status in MS is determined by gene-by-sex interactions. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 4 | 57% |
| Colombia | 1 | 14% |
| Unknown | 2 | 29% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 71% |
| Practitioners (doctors, other healthcare professionals) | 1 | 14% |
| Scientists | 1 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 43 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 7 | 16% |
| Researcher | 5 | 12% |
| Student > Master | 5 | 12% |
| Student > Ph. D. Student | 3 | 7% |
| Student > Postgraduate | 2 | 5% |
| Other | 5 | 12% |
| Unknown | 16 | 37% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 16% |
| Nursing and Health Professions | 5 | 12% |
| Neuroscience | 4 | 9% |
| Agricultural and Biological Sciences | 3 | 7% |
| Immunology and Microbiology | 2 | 5% |
| Other | 4 | 9% |
| Unknown | 18 | 42% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 20 August 2018.
All research outputs
#7,028,608
of 25,385,509 outputs
Outputs from Frontiers in immunology
#7,753
of 31,537 outputs
Outputs of similar age
#107,580
of 323,052 outputs
Outputs of similar age from Frontiers in immunology
#225
of 672 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 31,537 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has done well, scoring higher than 75% of its peers.
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 323,052 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 66% of its contemporaries.
We're also able to compare this research output to 672 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.