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Social Status is Associated with Impaired Anti-Inflammatory Response in Free-Ranging Male Rhesus Macaques

2023· article· en· W4385686756 on OpenAlexaff
Mitchell R. Sanchez Rosado, Laura Newman, Marina M. Watowich, Melissa A. Pavez-Fox, Josué Negron-Del Valle, Daniel Phillips, Macaela Skelton, Erin R. Siracusa, James P. Higham, Lauren J. N. Brent, Amanda J. Lea, Carlos A. Sariol, Noah Snyder‐Mackler

Bibliographic record

VenueThe Journal of Immunology · 2023
Typearticle
Languageen
FieldNeuroscience
TopicStress Responses and Cortisol
Canadian institutionsYork University
Fundersnot available
KeywordsImmune systemGlucocorticoidPeripheral blood mononuclear cellStimulationGene expressionImmunologyGeneBiologyInternal medicineEndocrinologyMedicineGeneticsIn vitro

Abstract

fetched live from OpenAlex

Abstract Exposure to social adversity can influence the onset and progression of disease. One possible mechanism through which social adversity may impact health outcomes is by altering immune homeostasis. Recently, evidence has connected social adversity to changes in gene regulation in the immune response of both humans and nonhuman primates. We investigated how social adversity (quantified as low social status) affected the Th2 immune response in free-ranging male rhesus macaques (n=128). We stimulated peripheral blood mononuclear cells (PBMCs) in vitro with Dexamethasone (Dex), an anti-inflammatory synthetic glucocorticoid (GC), and measured how social status influenced the gene regulatory response to Dex stimulation using mRNA-seq. We detected 2,923 differentially expressed genes (FDR<0.1) in response to Dex in PBMCs. After Dex stimulation, glucocorticoid responsive genes, such as FKBP5 and TSCD22, were induced and inflammatory genes, such as CSF1 and TNF, were repressed. Low social status animals had significantly higher mean expression of inflammatory genes (p=1.2×10−20) compared to high social status animals. Many of these genes, such as CD38 and NKAP, are known to be repressed by Dex. After Dex stimulation, low social status animals also had a higher mean expression (p=1.9×10−4) of genes related to the GC resistance-associated c-Myc/MAPK pathway. For instance, low social status animals had significantly higher expression (FDR<0.2) of signature genes in this pathway including AKT3, MAPK1 and PIK3CD. Our study suggests that the anti-inflammatory immune response in rhesus macaques can be negatively affected by low social status, with animals having a blunted response to Dex and presenting signatures of GC resistance. R01-AG060931 R00-AG051764 P40-OD012217

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.025
GPT teacher head0.276
Teacher spread0.251 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2023
Admission routes1
Has abstractyes

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