Extended Data Figure 5: Contribution of IL-1β to early MPN pathogenesis.

a, Increased BM IL-1β levels early in MPN. Multiplex ELISA analysis of pro-inflammatory (IL-1β, TNF-α, IFN-γ, IL-6), regulatory (IL-17) and anti-inflammatory (IL-10) mediators in plasma (control, n = 16; MPN, n = 13) and BM extracellular fluid samples (control, n = 11; MPN, n = 6; only IL-1β and TNF-α were detectable) from control and Mx1-cre;JAK2(V617F) mice 4–8 weeks after pIpC treatment. b–f, Nes-gfp mice were transplanted with BM cells from MPN (n = 6) and control (n = 3) mice and analysed 2 weeks later. b–d, mRNA expression of IL-1β (b) and its activating enzyme caspase-1 (Casp1, c), and BM frequencies of lin⁻sca-1⁺c-kit⁺ haematopoietic progenitors and CD11b⁺Ly-6G(1A8)⁻ monocytes (d). e, f, mRNA expression of IL-1 receptor (IL1r) (e) and its antagonist (IL1ra) (f) in BM CD45⁻CD31⁻Ter119⁻Nes-GFP^+/− cells. g, Number of circulating platelets in WT mice transplanted with MPN and control BM cells and treated over 18 weeks with IL1ra, starting 2 weeks after transplant. h, Frequency of BM CD45⁻CD31⁻Ter119⁻CD90⁺ cells in mice in g. i, j, qPCR analyses of IL-1β (i) and Casp1 (j) mRNA expression in haematopoietic progenitors and monocytes isolated from the BM of mice in g. Gapdh was used as housekeeping gene (n = 5). Mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001 (unpaired two-tailed t test).