biostudies-arrayexpressCheng-Chieh HsuMus musculushttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-15736Clonal hematopoiesis (CH) driven by Jak2V617F is known to accelerate atherosclerosis through inflammasome activation and release of IL-1β and IL-18, yet the specific contribution of IL-18 has remained unclear. In this study, we demonstrate that antibody inhibition of IL-18 in Jak2V617F CH mice increases plaque collagen but paradoxically promotes both early lesion growth and advanced necrotic core formation. Mechanistically, IL-18 blockade reverses AIM2 inflammasome activation but shifts cell death toward apoptosis, and together with impaired efferocytosis, results in greater necrosis. These events appear to be coordinated by reduced IFN-γ signaling, which enhanced collagen deposition while decreasing expression of efferocytotic genes.Our findings challenge the prevailing notion that IL-18 inhibition stabilizes atherosclerotic plaques in CH and provide new mechanistic insight into the interplay between inflammasome biology, adaptive immunity, and plaque stability.biostudies-arrayexpressSample Collection - Ldlr-/- mice received 20% Jak2VF BMT and received anti-IL-18 or IgG treatment for 16 weeks. After 16 weeks, the aortas were then carefully isolated and subjected to enzymatic digestion. Cells were stained and subject to flow cytometry sorting. Sorted live CD45+ cells were submitted to scRNA-seq sequencing.Sequencing - The prepared library was sequenced using NovaSeq 6000. Sequenced data were demultiplexed to generate the FASTQ files.Nucleic Acid Extraction - RNA was extracted using the 10x Genomics Chromium Single Cell 3' protocol.Library Construction - The library was constructed using the 10x Genomics Chromium Single Cell 3' protocol.OrganizationMINSEQE ScoreAssays and DataProcessed DataMAGE-TAB FilesData Transformation - FASTQ files were processed by Cell Ranger 8.0.1. Prebuilt reference mm10-2020-A (GENCODE vM23/Ensembl 98) was used for all samples.MetabolomicsUnknownTranscriptomicsGenomicsProteomicsIllumina NovaSeq 6000RNA-seq of coding RNA from single cellsMus musculusMojdeh TavallaieCheng-Chieh HsuAlan TallfalseIL-18 Inhibition Aggravates Atherosclerosis in Jak2V617F Clonal HematopoiesisClonal hematopoiesis (CH) driven by Jak2V617F is known to accelerate atherosclerosis through inflammasome activation and release of IL-1β and IL-18, yet the specific contribution of IL-18 has remained unclear. In this study, we demonstrate that antibody inhibition of IL-18 in Jak2V617F CH mice increases plaque collagen but paradoxically promotes both early lesion growth and advanced necrotic core formation. Mechanistically, IL-18 blockade reverses AIM2 inflammasome activation but shifts cell death toward apoptosis, and together with impaired efferocytosis, results in greater necrosis. These events appear to be coordinated by reduced IFN-γ signaling, which enhanced collagen deposition while decreasing expression of efferocytotic genes.Our findings challenge the prevailing notion that IL-18 inhibition stabilizes atherosclerotic plaques in CH and provide new mechanistic insight into the interplay between inflammasome biology, adaptive immunity, and plaque stability.2025-10-30T00:00:00Z2026-05-31T19:40:20.929Z2025-10-15T19:39:02.336ZE-MTAB-15736ERP182251EFO_0002944EFO_0004170EFO_0005684EFO_0005518EFO_0003816EFO_0004184