Fig. 8: Ifnar1^−/− knockout rescues Rnaset2^−/− related neuropathology.

a Immunohistochemistry of rescued cerebral T cell infiltration (CD3), interferon-stimulated gene 15 (ISG15) upregulation, microglial activation (TMEM119), and macrophages/activated microglia infiltration (MAC3) in Rnaset2^−/− Ifnar1^−/− mouse brain sections compared to control mouse and Rnaset2^−/− mouse brain sections. Scale bar, 20 µM and 1 mm for whole slices of ISG15. b Rescued cerebral inflammatory infiltration of CD3⁺ and MAC3⁺ cell densities determined in whole brain slices, TMEM119⁺ cell density of representative cortical regions, and % of immunoreactive area for ISG15 in Rnaset2^−/−Ifnar1^−/− (n = 6) compared to control (n = 5) and Rnaset2^−/− (n = 5). Images in a are representative for the 5–6 animals analyzed for each genotype. c T₂ relaxation time measurement in various brain regions of Rnaset2^−/−Ifnar1^−/− (n = 5), compared to control (n = 8) and Rnaset2^−/− (n = 8). For regions of interest (ROI) 1–4 selected for T₂ relaxation time measurements see Fig. 5d. IFNAR1-deficiency resolved extension of T₂ relaxation in Rnaset2^−/− mice. Data of two independent experiments. d Representative magnetic resonance anatomical images in axial plane showing ventricular enlargement in Rnaset2^−/− mice but not in Rnaset2^−/−Ifnar1^−/− mice due to shrinkage of the hippocampus on both sides (arrows). e Percent area of hippocampus (left and right) with respect to whole brain area of Rnaset2^−/− (n = 8), control (n = 8) and Rnaset2^−/− Ifnar1^−/− (n = 6). Data depicted as the mean ± SEM. p values of one-way ANOVA are represented as ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05 and not significant (ns) p ≥ 0.05. MRI data from Rnaset2^−/− and control mice are also depicted in Fig. 5c and d. Source data are provided as a Source data file.