Extended Data Fig. 6 ∣. JAK2^VF macrophages display increased NLRP3 and AIM2 inflammasome activation.

a, b, IL-1β was quantified in medium from mouse BMDMs treated with pdAdT for 6 h (a) or LPS (20 ng ml⁻¹; b) followed by a 1-h incubation with ATP (n = 6 biological replicates, representative of five experiments). Vertical P values are relative to LPS within the same genotype. c, d, IL-1β release from human iPSC-macrophages stimulated with pdAdT (c; n = 12 baseline, n = 6 treatments biological replicates representative of two experiments) and nigericin (d; n = 6 biological replicates, representative of two experiments). Vertical P values are relative to baseline within the same genotype. e, Immunoblot analysis of NLRP3 and AIM2 in protein lysates from BMDMs. f, g, Densiometric quantification of AIM2 (f) and NLRP3 (g; n = 8 biological replicates from four mice per group pooled together). h, Aim2 mRNA expression in BMDMs incubated in the presence of IFNY-neutralizing antibodies for 24 h (n = 6 biological replicates). i, Experimental scheme of atherosclerosis studies conducted in mice with Jak2^VF bone marrow deficient in Nlrp3 or Aim2. j, k, Plasma cholesterol following 12-week WTD in Jak2^VFNlrp3^−/− (j; n = 15 Jak2^VF, n = 19 Jak2^VFNlrp3^−/− mice) and Jak2^VFAim2^−/− mice (k; n = 24 Jak2^VF, n = 25 Jak2^VFAim2^−/− mice). l. Representative immunofluorescence image of aortic roots stained for DAPI (blue) and AIM2 (magenta). Yellow dashed lines, lesions; scale bars, 50 μm. m, Quantification of AIM2 mean fluorescence intensity in lesions (n = 16 control, n = 18 Jak2^VF mice). Mean ± s.e.m.; two-way ANOVA followed by Tukey’s post hoc test (a–d), one-way ANOVA followed by Tukey’s post hoc test (h), two-tailed t-test (j, k), two-tailed Mann–Whitney test (f, g, m).