Fig. 2: NK cells infiltrate the CNS and affect survival time in ALS models.

a Left: NKp46⁺ cells (in red) in cerebral slices of the lumbar spinal cord and motor cortex of hSOD1^G93A mice (13 weeks), not present in wt mice. Scale bar: 10 μm. 3d reconstruction of one representative NK cell on the right. Right: time course analysis of NK1.1⁺/CD3⁻ cells in the lumbar spinal cord and the cerebral motor cortex of hSOD1^G93A mice (mice at 8 and 19 weeks, n = 4; mice at 10, 13 and 16 weeks, n = 6. **P < 0.01, power 0.999, one-way ANOVA vs 8 weeks). b Frequency of NK1.1⁺/CD3⁻ cells in the spleen of wt and hSOD1^G93A mice (wt, n = 5; hSOD1^G93A n = 8). c Expression of GZMb, PRF and CD69 in the spleen and spinal cord of wt and hSOD1^G93A mice (wt, n = 3; hSOD1^G93A, n = 5, **P < 0.01, power 0.841, one-way ANOVA). d Distances of NKp46⁺ cells from vessel endothelial cells (CD31⁺ cells) in the spinal cord of hSOD1^G93A (13 weeks) mice (n = 4 mice/21 cells). Scale bar: 20 μm. Representative immunofluorescence is shown. e NK1.1⁺/CD3⁻ cells frequency in the motor cortex (top) and in the spinal cord (bottom) of hSOD1^G93A mice treated with Ab-CCL2 (n = 6, *P < 0.05 power 0.916 two-tailed Student’s t-test). Representative density plots are shown on the right. f Scheme of Ab-NK1.1 administration. g Kaplan–Meier curve of hSOD1^G93A and TDP43^A315T mice treated with vehicle or Ab-NK1.1 (hSOD1^G93A, vehicle: 136.8 ± 1.7 days; Ab-NK1.1: 147.2 ± 2.4 days; n = 5. TDP43^A315T, vehicle: 78.5 ± 1.5 days; Ab-NK1.1: 88.7 ± 1.9 days, n = 4. Data are the mean ± s.e.m. **P < 0.01, two-sided log-rank test). h Age of paralysis, calculated as the absence of hindlimb movement, upon Ab-NK1.1 treatment in hSOD1^G93A mice; vehicle: 18.3 ± 0.2 weeks; Ab-NK1.1: 19.5 ± 0.2 weeks (n = 7, data are the mean ± s.e.m. **P < 0.01 power 0.921 two-tailed Student’s t-test). For boxplots (a, c, e), the center line, boxes and whiskers represent the median, inner quartiles, and rest of the data distribution, respectively.