Abstract 641: Interleukin-15 Plays a Role in Atherosclerosis Through Effects on Multiple Inflammatory Cells in ApoE-/- Mice
Bibliographic record
Abstract
Objective: Interleukin (IL)-15 is a pro-inflammatory cytokine which is essential for the survival and maturation of natural killer (NK) and CD8+ T cells and has recently been reported to directly activate macrophages. In the present study, we used IL-15 overexpressing and IL-15 knockout mice to determine its effect on atherosclerosis in apolipoprotein E knockout (apoE-/-) mice. Approach and Results: Deficiency of IL-15 reduced atherosclerosis while overexpression of IL-15 increased atherosclerosis despite opposite effects on plasma lipoprotein cholesterol levels. Genetic ablation of IL-15 in apoE-/- mice resulted in a lack of NK cells and reduced populations of monocytes and CD8+ T cells, whereas overexpression of IL-15 had the opposite effects. CD8+ T cells were detected in atherosclerotic plaques from apoE-/- mice, were increased in plaques from il-15TgapoE-/- mice and were virtually absent from plaques from il15-/- apoE-/- mice. To test the role of NK, NKT and activated CD8+ T cells in atherosclerosis, NK1.1+ cells were immuno-depleted from apoE-/- mice. Atherosclerosis was reduced but to a lesser extent than in age matched il15-/- apoE-/- mice. Plaques from these mice, however, were almost devoid of CD8+ T cells. ApoE-/- mice that were heterozygous for IL-15 (il15+/-apoE-/-) exhibited normal levels of NK, NKT, CD8T cells and monocytes however atherosclerosis was reduced by 40-50 % compared to control apoE-/- mice. This suggested that IL-15 also affects atherosclerosis through NK/NKT and CD8+ T cell independent pathways. Treatment of macrophages with recombinant IL-15 in vitro induced inflammatory cytokines and foam cell formation. Furthermore, reduced levels of MCP-1 and CD11b immune-reactivity were detected in plaques from il15-/- apoE-/- compared to control apoE-/- mice. Conclusions: IL-15 plays a significant role in promoting atherosclerosis through pathways affecting multiple inflammatory cells including the survival/recruitment of NK, NKT and CD8+ T cells, the modulation of monocyte levels, and direct activation of macrophages.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.003 |
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".