PS-B12-3: ANGIOTENSIN II CAUSED ACTIVATED DNKT CELL EXPANSION IN MESENTERIC VESSEL PERIVASCULAR ADIPOSE TISSUE OF MALE MICE
Bibliographic record
Abstract
Objective: We have demonstrated that γΔ T cells, which are an innate-like T cell subset mostly found in tissues, play a role in hypertension. We showed that angiotensin (AngII) II-induced γΔ T cell expansion in perivascular adipose tissue (PVAT), hypertension and mesenteric artery endothelial dysfunction that were blunted in mice deficient in γΔ T cells. We hypothesized that single cell RNA sequencing (scRNA-seq) would reveal γΔ T cell subpopulations in PVAT involved in hypertension, vascular injury and T cell activation. Design and method: Male C57BL/6J mice were infused SC or not with 490 ng/kg/min AngII for 14 days (n = 3). Hypertension was confirmed by tail cuff blood pressure measurement. Mesenteric vessels (MV) with PVAT were collected, lymph nodes removed, single cell suspension obtained, samples labeled with hashtag antibodies, T cells isolated by fluorescence-activated cell sorting, the 6 samples pooled in one tube, scRNA libraries prepared with a Chromium Next GEM Single Cell 3 Reagent Kit. Sequencing was done on an Illumina Novaseq 6000, and sequences were mapped to mouse genome mm10–2020-A, data analysed using Cell Ranger pipeline and Seurat in R. Gene ontology (GO) term enrichment analysis done by Cytoscape. Cell subpopulations were validated by flow cytometry using a BD LSR Fortessa cell analyzer and data analyzed using FlowJo software. Results: SBP of mice was increased in AngII (141 ± 11 mm Hg) vs sham-treated mice (108 ± 2 mm Hg). ScRNA-seq yielded 5,030 cells with 137,990 reads/cell and identified 11 T cell clusters. GO term enrichment analysis revealed that CD8+ natural killer T (NKT), NKT1, γΔ T and T regulatory cell clusters have differentially expressed genes associated with immune cell activation and stress response. Subclustering of T cells expressing the T cell receptor (TCR) Δ constant chain (Trdc) revealed 3 ΔNKT (ΔNKT0, ΔNKT1 and activated ΔNKT cells) and 3 γΔ T cell subpopulations (Trgc1low effector memory, TCR Δ variable 4+ and apoptotic γΔ T cells). AngII increased > 2-fold the frequency of activated ΔNKT cells, and decreased by 74% ΔNKT0 cells. Gene expression profiling revealed that activated ΔNKT and ΔNKT0 cells could be identified using unique markers among Trdc+ cell population, Cd28 and Sell, respectively. Flow cytometry showed that TCRΔ+CD28+Sell- T cells were 1.7-fold increased and TCRΔ+CD28-Sell+ T cells decreased by 52% in MV-PVAT of AngII vs sham-treated mice. Conclusion: This study identified an activated ΔNKT cell subpopulation in MV-PVAT that may play a role in AngII-induced hypertension, vascular injury and T cell activation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".