Abstract 80: Interleukin 15 Plays an Important Role in the Development of Atherosclerosis in Apolipoprotein E Knockout Mice
Bibliographic record
Abstract
IL-15 is an essential cytokine for the development of NK and CD8+T cells and also involved in activation of inflammation in macrophages. Therefore, we hypothesized that IL-15 may affect the development of atherosclerosis via regulating immune/inflammatory cells. To test this we generated apoE KO mice that either overexpressed (il-15TgapoE-/-) or lacked either one (il-15+/-apoE-/-) or both copies (il-15-/-apoE-/-) of the IL-15 gene. Deficiency of IL-15 substantially reduced atherosclerosis in spite of increased plasma lipoprotein cholesterol levels. Interestingly, il-15+/-apoE -/- mice exhibited intermediate levels of atherosclerosis. Conversely, overexpression of IL-15 in il-15tg apoE -/- mice resulted in substantially increased atherosclerosis compared to apoE -/- littermates. Deficiency of IL-15 resulted in a lack of NK cells and reduced populations of monocytes and CD8+ T cells. Correspondingly, reduced levels of CD11b+ and CD8a+ cells were detected in atherosclerotic lesions from il-15-/-apoE -/- mice compared to those from apoE -/- mice. To test the role of NK cells in atherosclerosis, NK1.1+ cells were immune-depleted in apoE -/- mice and lesions size was analyzed. Atherosclerosis was reduced but to a lesser extent than in age matched il-15-/-apoE -/- mice. Plaques from these mice were almost devoid of CD8+T cells. Deletion of a single copy of the il-15 gene (il-15+/-) in NK/NKT cell immunodepleted apoE -/- mice resulted in a further reduction in atherosclerosis, suggesting the involvement NK/NKT and CD8-T cell independent pathways participate in IL-15’s proatherogenic effects. Treatment of macrophages with recombinant IL-15 in vitro induced expression/activity of a variety of pro-inflammatory targets. Furthermore, il-15-/-apoE -/- mice exhibited reduced levels of MCP-1 in plaques and reduced circulating levels of SAA and IL-6, whereas circulating levels of SAA and IL-6 were greatly increased in il-15tg apoE -/- mice compared to apoE -/- littermates. In conclusion IL-15 plays a significant role in promoting atherosclerosis through multiple pathways including promotion of the survival/recruitment of NK/CD8+T cells, as well as the modulation of monocyte levels, and/or direct activation of macrophages.
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 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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 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".