IL-1α–IL-1R1 axis directly drives Tet2^+/− clonal expansion via increased multilineage differentiation. (A) Experimental design. (B) Longitudinal quantification of the percentage of CD45⁺ WT ZsG⁺ and CD45⁺Tet2^+/− ZsG⁺ in PB of mice exposed to PBS or IL-1α (n = 2-5). (C) Longitudinal assessment of the percentage of WT or Tet2^+/− ZsG⁺ cells in PB T cells, B cells, and myeloid cells of mice exposed to PBS or IL-1α (n = 4-6). Blue boxes on x-axis indicate IL-1α exposure period. (D) Terminal assessment of the percentage of WT or Tet2^+/− ZsG⁺ cells in indicated BM populations of mice exposed to PBS or IL-1α (n = 4-6). (E) Experimental design. (F) Longitudinal quantification of the percentage of CD45.2⁺ WT and CD45.2⁺Tet2^+/− in PB of mice exposed to PBS or IL-1α (n = 5-6). Blue boxes on x-axis indicate IL-1α exposure period. (G) Percentage of WT or Tet2^+/− CD45.2⁺ cells in PB T cells, B cells, and myeloid cells of mice exposed to PBS or IL-1α (n = 5-6). (H) Percentage of WT or Tet2^+/− CD45.2⁺ cells in indicated BM populations of mice exposed to PBS or IL-1α (n = 5-6). (I) Experimental design. (J) Longitudinal quantification of the percentage of CD45.2⁺ WT; Ilr1^–/– and CD45.2⁺Tet2^+/−; Ilr1^–/– cells in PB of mice exposed to PBS or IL-1α (n = 5-6). Blue boxes on x-axis indicate IL-1α exposure period. (K) Percentage of CD45.2⁺ WT; Ilr1^–/– and CD45.2⁺Tet2^+/−; Ilr1^–/– cells in PB T cells, B cells, and myeloid cells of mice exposed to PBS or IL-1α (n = 5-6). (L) Percentage of CD45.2⁺ WT; Ilr1^–/– and CD45.2⁺Tet2^+/−; Ilr1^–/– cells in indicated BM populations of mice exposed to PBS or IL-1α (n = 5-6). ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, and ∗∗∗∗P < .0001 by unpaired t-test (between PBS and IL-1α conditions, within the same genotype for C, D, G, H, K, and L) or by a 1-way analysis of variance with Tukey correction (for last time point in B, F, and J). Error bars represent standard error of the mean. WBM, whole bone marrow.