Fig. 8: Type I interferon receptor (IFNAR) blockade may improve CSD-stress related behavioral anhedonia and prevent meningeal neutrophil accumulation.

a Schematic showing drug-delivery schedule for IFNAR blocking antibodies. Mice were injected with either matched IgG control antibody or anti-IFNAR antibody on the days indicated with yellow arrows. b USM results from LysM^gfp/+ mice; see Fig. S22 for comparison with HC+IgG mice and for more detail. CSD+anti-IFNAR treated mice showed behavioral improvement compared to CSD+IgG mice (Mann Whitney, *p = 0.014, U = 36, Hodges-Lehmann estimate=21.35, n_CSD+IgG = 12, n_CSD+IFNAR = 12. N = 5 experiments). Hereafter we considered these LysM^gfp/+ mice as two separate groups – those that marked in the USM test (+, indicated with closed circles) and those that didn’t (-, indicated with open circles). cLeft: CSD+anti-IFNAR(+) mice showed improvement in the OF task for anxiety-like behavior compared to CSD+IgG-treated mice (*p = 0.046, t = 2.2, df = 16, 95% CI [0.10, 9.40]). Right: No improvement in OF behavior overall for CSF+anti-IFNAR-treated mice. n_CSD+IgG = 12, n_CSD+IFNAR = 12 (within IFNAR-treated, n_USM+=6, n_USM-=6). dTop: Representative images for dorsal whole-mount meningeal tissue from CSD+IgG and CSD+anti-IFNAR treated mice. Scale bar = 1 mm. Bottom: Images from HC and CSD mice showing hand-counted LysM-GFP⁺ cells, normalized to indicated area. e Left: Quantification of total nonvascular (>10μm away from a blood vessel) meningeal LysM-GFP⁺ cells shows reduced myeloid cell accumulation in CSD+anti-IFNAR(+) treated mice (*p = 0.048, t = 2.2, df = 11, 95% CI [−0.69, −0.0043]). Right: No improvement in LysM-GFP⁺ cells accumulation overall for CSF+anti-IFNAR-treated mice. n_CSD+IgG = 9, n_CSD+IFNAR = 10 (within IFNAR-treated, n_USM+=4, n_USM-=6). ^†square root^-transformed values. f In C57BL/6 J wild type mice there was an IFNAR-mediated rescue in meningeal neutrophil accumulation following CSD stress, with expected differences in IgG control groups (2-way ANOVA, *P = 0.033, F_(1,27) = 5.0, n_CSD+IFNAR = 7, otherwise n = 8. N = 2 experiments). See Table S11 for post-hoc statistics. Significance levels shown are from post-hoc testing adjusted for multiple comparisons. There was no effect of anti-IFNAR treatment on iv⁺ meningeal or blood neutrophils or other cell types; see Fig. S23. Data points represent individual mice. Two-tailed tests were used in (b, c, e); all tests were unpaired t tests unless otherwise indicated. CSD = chronic social defeat, HC = home cage. Data shown as mean ± SEM. *p < 0.05, **p < 0.01. Source data provided in Source Data file. Schematics from BioRender. Kigar, S. (2025) https://BioRender.com/rvrmii4.