Fig. 4: Damage-resistant IL-18R⁺ NK cells suppress thymus repair.

a, CellChat interaction analysis for IL-18 at baseline and following SL-TBI, taken from the scRNAseq dataset described in Fig. 2a, with quantification of the aggregate signal strength for each IL-18 target cell. b–d, Female 1- to 2-month-old C57BL/6 CD45.2⁺ mice were lethally irradiated and transplanted (i.v.) with 5 × 10⁶ WT CD45.1⁺ bone marrow cells. b, Concatenated flow cytometry plots showing CD45⁺CD45.1⁻CD4⁻CD8⁻ cells (top) and CD45⁺CD45.1⁻CD4⁻CD8⁻NK1.1⁺IL-18R⁺ cells gated on CD3⁺ NKT cells and CD49b⁺ NK cells (bottom) from thymus-recipient mice at the indicated time points after HCT (n = 4–7 per time point). c,d, Proportion (c) and total number (d) of recipient NK or NKT cells before HCT (day 0; n = 7) and on days 1, 3, 7 and 14 after HCT (n = 4 per group). e, Thymuses of female 1- to 2-month-old C57BL/6 mice were visualized at steady state or on day 3 or 7 after SL-TBI at 12×, assessing keratin-14-positive (Krt14⁺) mTECs (green), keratin-8-positive (Krt8⁺) cTECs (pink) and NKp46⁺ NK cells (arrows). The NKp46⁺ NK/ILC1 cell distribution within the thymus cortex or medulla at 0, 3 and 7 days after SL-TBI is shown (n = 3 per group). f, Female 1- to 2-month-old WT C57BL/6 mice were administered 200 μg of anti-NK1.1 mAb or control PBS (i.p.) on days −1, 1 and 3 after SL-TBI, and thymus cellularity was assessed on day 7 (n = 9 per group). g, Female 1- to 2-month-old C57BL/6 WT, Il18^−/− and Il18r1^−/− mice were administered 200 μg of anti-NK1.1 mAb or isotype/PBS (i.p.) as above. The relative change in thymus cellularity is shown, comparing control-treated (WT, n = 17; Il18^−/−, n = 9; Il18r1^−/−, n = 8) and anti-NK1.1 mAb-treated (WT, n = 21; Il18^−/−, n = 8; Il18r1^−/−, n = 9) mice within each strain 7 days after SL-TBI. h, Female 1- to 2-month-old C57BL/6 WT (Cd1d^+/+, n = 9) and Cd1d^−/− (n = 6) mice were exposed to SL-TBI, and thymus cellularity was measured 7 days later. i, Female 1- to 2-month-old Il18r1^fl/fl:Lck-Cre⁻ (Il18r1^WT, n = 5) and Il18r1^fl/fl:Lck-Cre⁺ (Il18r1^ΔT/NKT, n = 5) mice were exposed to SL-TBI and administered rIL-18 (s.c., 2.5 mg kg⁻¹) on day 3. Thymus cellularity was measured on day 7 after SL-TBI. j, Female 1- to 2-month-old Il18r1^fl/fl:Ncr1-Cre⁻ (Il18r1^WT, n = 6) and Il18r1^fl/fl:Ncr1-Cre⁺ (Il18r1^ΔNK/ILC1, n = 7) mice were exposed to SL-TBI and administered rIL-18 (s.c., 2.5 mg kg⁻¹) on day 3. Thymus cellularity was measured on day 7 after SL-TBI. Graphs represent mean ± s.e.m.; each dot represents an individual biological replicate. Statistics were generated for c and d using one-way ANOVA with Dunnet’s correction for multiple comparisons, for e using one-way ANOVA with Tukey’s correction for multiple comparisons, and for f–j using unpaired two-tailed t tests.

Source data