Journal: Neuron

Article Title: Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy

doi: 10.1016/j.neuron.2026.08.030

Figure Lengend Snippet: (A) Representative flow cytometry plots showing lymphocyte (upper row) and T cell (middle and bottom rows) populations in E4 PBS, TE4 IgG, and TE4 anti-CXCR3 (aCXCR3)-treated mice following ICHC-IFN γ . (B-G) , Flow cytometry quantification of total CD45 med CD11b hi microglia ( B ), Nk1.1 + NK cells ( C ) Nk1.1 + TCRb + NKT cells ( D ), total T cells ( E ), CD4 + ( F ) and CD8 + T cells ( G ) in brains of ICHC-IFN γ –treated mice receiving IgG isotype control or aCXCR3 and a 9.5-month-old TE4 untreated positive control (n=4-7). (H) Representative immunofluorescence images illustrating CD3, CD8, and CD4-positive T cells in the hippocampus from IFN-γ–treated mice receiving IgG or aCXCR3. Scale bar, 200 μm. (I) Quantification of the number of CD3-positive T cells in the hippocampus, as illustrated in (H) (n=3-8). Data plotted as mean ± SEM.

Article Snippet: Anti-mouse CXCR3 Neutralizing Antibody (Clone CXCR3-173) , BioXCell , Cat# BE0249; RRID:AB_2687730.

Techniques: Flow Cytometry, Control, Positive Control, Immunofluorescence

Journal: Neuron

Article Title: Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy

doi: 10.1016/j.neuron.2026.08.030

Figure Lengend Snippet: (A) Schematic outlining administration of anti-CXCR3 (aCXCR3) or IgG control antibody in TE4 mice over three and a half months, including treatment timeline and experimental endpoints. ( B ) Representative high magnification images containing CD31, CD3 and anti-Armenian hamster (to label aCXCR3 treatment antibody), illustrating binding of the mAB to T cells on border tissues such as the ( i ) choroid plexus and ventricular space as well as on T cells in contact with vessels in the brain ( ii ). This binding was not observed in parenchymal T cells ( iii ). Scale bar = 100 μm. (C) Representative immunofluorescence images illustrating CD3, CD4 and CD8-positive T cells in brains of TE4 IgG– and TE4 aCXCR3–treated mice. Scale bar = 200 μm. (D) Quantification of CD3, CD4, and CD8-positive T cells in the hippocampus (n=4-15). (E) Representative immunofluorescence images of the dentate gyrus immunostained with NeuN from TE4 IgG– and TE4 aCXCR3–treated mice. (F) Quantification of dentate gyrus layer thickness and NeuN-positive neuron number (n=8-15). (G) Representative cresyl violet–stained coronal brain sections from E4 and TE4 mice treated with IgG or aCXCR3, illustrating a marked reduction in neurodegeneration from aCXCR3. (H) Quantification of hippocampal, ventricular, and entorhinal/piriform cortex volumes from cresyl violet–stained sections , analyzed separately for male (top row) and female mice (bottom row) (n=9-15).

Article Snippet: Anti-mouse CXCR3 Neutralizing Antibody (Clone CXCR3-173) , BioXCell , Cat# BE0249; RRID:AB_2687730.

Techniques: Control, Binding Assay, Immunofluorescence, Staining, FACS, Immunohistochemistry

Journal: Neuron

Article Title: Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy

doi: 10.1016/j.neuron.2026.08.030

Figure Lengend Snippet: (A) Representative immunofluorescence images of AT8-immunoreactive phosphorylated tau in the hippocampus of TE4 mice treated with IgG or aCXCR3. Scale bar, 250 μm. (B) Quantification of tau pathology expressed as percent area of AT8 immunoreactivity analyzed separately for male (top row) and female mice (bottom row) (n=4-15). (C) Biochemical analysis of Sarkosyl soluble and insoluble tau in hippocampal tissue from TE4 IgG– and TE4 aCXCR3–treated mice (n=8-11). (D) Quantification of plasma neurofilament light chain (NfL) levels in TE4 IgG– and TE4 aCXCR3–treated mice (n=4-11). (E) Quantification of interaction time during the novel object recognition (NOR) task in TE4 IgG– and TE4 aCXCR3–treated mice, analyzed separately for male and female mice (n=13-18). Data are mean ± SEM. Scale bar, 250 μm.

Article Snippet: Anti-mouse CXCR3 Neutralizing Antibody (Clone CXCR3-173) , BioXCell , Cat# BE0249; RRID:AB_2687730.

Techniques: Pathology, In Vivo, Immunofluorescence, Analysis, Tissue, Clinical Proteomics

Journal: Neuron

Article Title: Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy

doi: 10.1016/j.neuron.2026.08.030

Figure Lengend Snippet: (A) Representative immunofluorescence images of the hippocampus illustrating a panel of microglial markers Iba1, P2ry12, Clec7A, MHCII, and Tmem119 in TE4 mice treated with IgG or aCXCR3. Higher-magnification insets highlight marker expression in the dentate gyrus. Scale bar, 250 μm (main panels) and 100 μm (insets). (B) Quantification of microglial marker expression analyzed separately for male and female mice (n=8-16). (C) Representative immunofluorescence images of the dentate gyrus illustrating a panel of astrocytic markers GFAP, S100B, and CXCL10 in TE4 mice treated with IgG or aCXCR3. Higher-magnification insets of the dentate gyrus are shown. Scale bar, 250 μm (main panels) and 100 μm (insets). (D) Quantification of astrocytic marker expression analyzed separately for male and female mice (n=5-16). ( E ) Quantification of brain IFNγ levels in male and female mice by ELISA (n=9-11). ( F ) Quantification of plasma CXCL10 by ELISA (n=6, circles = males, squares = females). Data plotted as mean ± SEM.

Article Snippet: Anti-mouse CXCR3 Neutralizing Antibody (Clone CXCR3-173) , BioXCell , Cat# BE0249; RRID:AB_2687730.

Techniques: Immunofluorescence, Marker, Expressing, Enzyme-linked Immunosorbent Assay, Clinical Proteomics

Journal: Neuron

Article Title: Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy

doi: 10.1016/j.neuron.2026.08.030

Figure Lengend Snippet: (A) Uniform manifold approximation and projection (UMAP) of scRNAseq data from CD45 hi FACS-sorted T cells isolated from brains of male (mTE4) and female (fTE4) TE4 mice treated with IgG or aCXCR3, with cluster annotations. Cluster identities were defined based on canonical marker gene expression and are displayed in Figure S7 . Feature plots illustrate expression of Cd8a and Cd4-positive clusters. (B) UMAP visualization of CD8 + T cells subsets, with cluster annotations. (C) UMAP visualization of CD4 + T cells subsets, with cluster annotations. (D) Proportion plot of CD8 + T cell subtypes in IgG- and aCXCR3-treated TE4 mice, as defined by transcriptional clustering between male and female datasets, to illustrate an increase in the proportion of Exhausted (Pdcd1 + Tox + Tigit + ) with slight reductions in cytotoxic (Gzmk + Eomes + ) and activated-effector (Tox + Tigit + Ccl5 + ) CD8 + T cells in aCXCR3-treated mice. (E) Proportion of CD4 + T cell subtypes in IgG- and aCXCR3-treated TE4 mice, illustrating a marked reduction in naïve (Slamf6 + , S1pr1 + ), interferon-responsive (Ifit3 + Isg15 + ), activated Th1-like (Cxcr3 + Xcl1 + Cd40lg + ) in aCXCR3-treated mice (n=2 pooled samples per group).

Article Snippet: Anti-mouse CXCR3 Neutralizing Antibody (Clone CXCR3-173) , BioXCell , Cat# BE0249; RRID:AB_2687730.

Techniques: Isolation, Marker, Gene Expression, Expressing

Journal: Neuron

Article Title: Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy

doi: 10.1016/j.neuron.2026.08.030

Figure Lengend Snippet: (A) Representative gating strategy illustrating the exclusion of dead and peripherally labelled circulating CD45 + cells, and inclusion of T cell subpopulations like Th1 and exhausted CD8 T cells. ( B ) Quantification of flow analysis total, CD4 + and CD8 + T cells as a percentage of live singlets( C ) Quantification of the bead-normalized number of T-bet + IFNγ + T cells (Th1). ( D ) Quantification of CD8 + T cell exhausted subpopulations as a percentage of CD8 or total Tex (n=14-17). Circles = males, squares = females. Data plotted as mean±SEM.

Article Snippet: Anti-mouse CXCR3 Neutralizing Antibody (Clone CXCR3-173) , BioXCell , Cat# BE0249; RRID:AB_2687730.

Techniques: Analysis

Journal: Bioactive Materials

Article Title: Microenvironment-educated MSC-EVs loaded injectable smart hydrogel for targeting senescent nucleus pulposus cells and inhibiting ferroptosis against intervertebral disc degeneration

doi: 10.1016/j.bioactmat.2026.02.030

Figure Lengend Snippet: Targeting Capability of D-EVs to Senescent NPCs is Mediated by the CXCL10-CXCR3 Axis. (A) Schematic diagram of RNA sequencing for senescent NPCs treated with D-EVs or not. (B-C) Volcano plots and heatmaps displaying differential gene expression in senescent NPCs treated with D-EVs or not. (D) A Venn diagram illustrates overlap between DEGs identified in senescent NPCs treated with D-EVs and key gene databases for cytokine-cytokine receptor interactions. (E) A Venn diagram illustrates overlap between DEGs identified in D-MSCs and chemokine signaling pathway key gene databases. (F-G) Network analysis of the hub genes among the above total DEGs. A protein-protein interaction network was created in the STRING database, while the Cytoscape software was used to determine the hub genes in the network. (H) GO analysis confirming enrichment of terms related to senescent NPCs treated with D-EVs or not in the BP categories. (I) GSEA analysis of cytokine-cytokine receptor interactions in D-EVs group versus TBHP group. (J) Western blot analysis confirmed the expression of CXCR3 in Control and senescent NPCs, and (S) quantitative analysis. (K) Western blot analysis confirmed the expression of CXCL10 in N-EVs and D-EVs, and (R) quantitative analysis. (L) Protein binding analysis of CXCR3 and CXCL10 by PyMOL. (M) Confocal analysis of the uptake of pHrodo-labeled EVs in senescent NPCs following the treatments of N-EVs, D-EVs with CXCL10 knockout/anti-CXCR3, or not, and (Q) quantitative analysis. (N) In vivo tracking of PKH26-labeled CXCL10 knockout D-EVs. (O) Flow cytometry showing uptake of different EVs with CXCL10 knockout/anti-CXCR3 or not by senescent NPCs, and (P) quantitative analysis. The data were presented as mean ± SD. n = 3, ns, not significant; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.

Article Snippet: After blocked with 5% non-fat milk for 2 h at room temperature, the membranes were incubated with primary antibodies against GAPDH (1:5000, 104941-AP, Proteintech), TSG101 (1:1000, DF8427, Affinity), CD9 (1:1000, AF5139, Affinity), CD63 (1:2000, 25682-1-AP, Proteintech), Calnexin (1:5000, 10427-2-AP, Proteintech), GM130 (1:20000, 11308-1-AP, Proteintech), CXCR3 (1:5000, 26756-1-AP, Proteintech), CXCL10 (1:2000, 10937-1-AP, Proteintech), MMP3 (1:2000, 17873-1-AP, Proteintech), ADAMTS5 (DF13268, Affinity), P16 (AF5484, Affinity), P21 (10355-1-AP, Proteintech), GPX4 (1:1000, 381958, Zen-bio), SLC7A11 (1:1000, 26864-1-AP, Proteintech), ACSL4 (1:5000, 22401-1-AP, Proteintech) and Tubulin (1:10000, T40103 , Abmart) overnight at 4 °C.

Techniques: RNA Sequencing, Gene Expression, Software, Western Blot, Expressing, Control, Protein Binding, Labeling, Knock-Out, In Vivo, Flow Cytometry