Fig. 1: Chronic IL1β exposure enhances the expansion of Tet2-KO cells and myeloid bias with the elevation of Ly6c^hi over Ly6c^lo monocytes/macrophages.

a–c Lineage-depleted BM cells from wild-type (WT) CD45.1 and Tet2-KO CD45.2 mice were transplanted into WT CD45.1/2 mice which after 3 weeks were treated with IL1β or vehicle daily. a Experimental design, b percentage of WT CD45.1 or Tet2-KO CD45.2 cells out of all CD45⁺ cells (chimerism, significance shown between Tet2-KO with and without IL1β treatment) and the percentage WT CD45.1 and Tet2-KO CD45.2⁺ cells which are myeloid in the PB (significance shown between Tet2-KO and WT with IL1β treatment, n = 5 mice/group for Veh, 6 for IL1β) and c myeloid subsets (CD11b⁺Gr1^hi, CD11b⁺Gr1^lo) at week 15 (n = 5 mice/group for Veh, 4 for IL1β). d–f Lineage-depleted BM cells from WT CD45.1⁺ and Rosa-rtTA-driven inducible Tet2 knockdown (shTet2) CD45.2 mice were transplanted into WT CD45.1⁺CD45.2⁺ mice, treated with doxycycline (dox) two weeks after transplantation and IL1β or vehicle three weeks after transplantation for increasing intervals up to 10 weeks and then with and without doxycycline (withdrawal; w/d) for an additional two weeks. Arrows indicate the time relative to the initial treatment (week: 0, 3, 6, 8) and duration (days: 2, 4, 7, and 28) of daily treatment with IL1β or vehicle. Green indicates time and duration of doxycycline treatment. d Experimental design, e percentage of GFP⁺CD45.2 cells out of donor-derived CD45⁺ cells and the percentage of WT CD45.1 and shTet2 CD45.2 cells which are myeloid (CD11b⁺) in the PB for doxy and IL1β or vehicle-treated experimental arms (significance shown between shTet2 and WT with IL1β treatment, right panel, n = 5 mice/group), and f neutrophils (CD11b⁺Ly6c^midLy6g⁺), Ly6c^hi monocytes/macrophages (CD11b⁺Ly6c^hiLy6g^-), and Ly6c^lo monocytes/macrophages (CD11b⁺Ly6c^loLy6g^-) in the spleen with doxy or without doxy (w/d) for IL1β or vehicle treatments (n = 5 mice/group for Veh, IL1β, Dox w/d IL1β, 4 for Dox w/d mice/group). Error bars represent mean ± SEM. For panels c and f two-factor ANOVA determined family-wise error rate (FWER) adjusted p values. For panels b and e, a student’s two-tailed t-Test determined the significance between single comparisons. For FWER adjusted and regular p values: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.