Extended Data Fig. 9: Aortic inflammasome activation in Ldlr−/−Tet2−/−BM and Ldlr−/−p53−/−BM mice exposed to SF and extended analysis of CLEC4E signaling.
From: Mutation-dependent responses to sleep and exercise in clonal haematopoiesis
Immunofluorescence staining of atherosclerotic plaques in Ldlr−/−Tet2−/−BM (a) and Ldlr−/−p53−/−BM (b) mice exposed to SF or sedentary lifestyle. Sections were stained for IL-1β, AIM2, and NLRP3, with Mac-2 as a counterstain to identify macrophages. Representative images are shown for each condition; scale bars are 400 µm. For Ldlr−/−Tet2−/−BM, n = 6, 6 (IL-1β) and 7, 7 (AIM2/NLRP3) for Sedentary vs SF. For Ldlr−/−p53−/−BM, n = 9, 9 (IL-1β, AIM2) and 8, 9 (NLRP3) for Sedentary vs SF. (c) UMAP of reclustered CD45.2 macrophages from single cell RNA sequencing of the aorta, integrating all cells across four conditions. Clec4e expression is visualized as a heat map overlaid per cell. Adjacent violin plot depicts Log2-transformed Clec4e expression across the four macrophage sub-clusters identified in the UMAP. n = 5 pooled mice. d. IL-1β in the supernatant of WT BMDMs with Clec4e agonism (TDB) or antagonism (n = 6 technical replicates control, 6 anti-CLEC4E, 6 anti-CLEC4E + TBD). e. Body weights and plasma lipids in Ldlr−/−Jak2V617FBM mice treated with either saline or anti-CLEC4E antibody and exposed to either SF or sedentary lifestyle at the time of euthanasia (n = 7, 7 sedentary + saline; 7,7 sedentary + anti-CLEC4E; 6, 6 SF + saline and 6, 5 SF + anti-CLEC4E for body weight and plasma lipids, respectively). Two-sided statistics. Data are mean ± s.e.m; ns = not significant, * p < 0.05, **** p < 0.0001. P-values were obtained from individual Mann–Whitney U tests (a) or ordinary one-way ANOVA (d). Schematic in panel e created in BioRender; McAlpine, C. https://biorender.com/1rt7rau (2026).
