التفاصيل البيبلوغرافية
| العنوان: |
Abstract P125: IL-6-induced Signaling In PD-1 + CD4 Effector Memory T Cells Is Associated With Human Coronary Pathology |
| المؤلفون: |
Kothari, Hema, McSkimming, Chantel, Drago, Fabrizio, Williams, Corey, Zunder, Eli, McNamara, Coleen |
| المصدر: |
Arteriosclerosis, Thrombosis, and Vascular Biology ; volume 41, issue Suppl_1 ; ISSN 1079-5642 1524-4636 |
| بيانات النشر: |
Ovid Technologies (Wolters Kluwer Health) |
| سنة النشر: |
2021 |
| الوصف: |
Objective: Murine data, prospective epidemiological studies, and genetic association data support a potential causal role of IL-6 signaling in atherosclerosis development. IL-6 inhibitors have emerged as potential therapeutics for reducing events in both stable coronary artery disease (CAD) and acute coronary syndromes. IL-6-induced immune regulation plays an important role in atherosclerosis, however, a comprehensive map of IL-6 signaling in human immune cells is currently lacking. We developed a 32-antibody custom mass cytometry (CyTOF) panel to characterize IL-6 signaling across all major human immune cell subsets and applied it to identify IL-6-induced immune signatures linked with unstable atherosclerotic plaque. Methods: Peripheral blood mononuclear cells from healthy donors and subjects with CAD undergoing virtual histology-intravascular ultrasound imaging (IVUS-VH) were stimulated with vehicle and IL-6, stained, and ran in CyTOF. Unsupervised analysis algorithms (SPADE, UMAP, and Leiden clustering) were used to identify immune cell subsets and IL-6-induced intracellular phosphorylation status. Results: IL-6 induced STAT1 and STAT3 activation in CD4 and CD8 naïve T cell subsets and CD4 memory T subsets. Notably, we identified that IL-6 also activates STAT5 within the CD4 and CD8 naïve T subsets. IL-6 induced a much more robust activation of STAT1 as compared to STAT3 and STAT5. Other cell types such as CD14 + monocytes, and CD11c + , and CD123 + dendritic cells also showed IL-6-induced STAT activation. IL-6-induced phosphorylation of STAT1 and STAT3 in a novel PD-1 + CD4 + effector memory T cell subtype was associated with higher CAD burden and unstable plaque features. Conclusions: Findings are significant for mechanistic insights into IL-6-induced inflammation and may enable discovery of new approaches to reduce inflammation in CAD and other pathologies. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1161/atvb.41.suppl_1.p125 |
| الاتاحة: |
http://dx.doi.org/10.1161/atvb.41.suppl_1.p125 |
| رقم الانضمام: |
edsbas.51CDC08B |
| قاعدة البيانات: |
BASE |