Journal: Journal of Translational Autoimmunity

Article Title: T cell proliferative response to a homocitrullinated peptide correlates with joint pathology in collagen induced arthritis

doi: 10.1016/j.jtauto.2025.100345

Figure Lengend Snippet: Phenotypic Characterization of Collagen Induced Arthritis in DBA/1J Mice. DBA/1J mice were immunized with bovine type II collagen (N = 11–55; arthritic: n = 6–18; non-arthritic: n = 5–37) or PBS (N = 4–14). A) Representative photographs and E) 3D-rendered micro-CT radiographs of arthritic (red arrow = bone erosion), non-arthritic, and PBS-injected mouse hind limbs. Changes in B) clinical arthritis score, C) anti-bovine type II collagen (CII) IgG and D) anti-mouse CII IgG over time. Dashed line represents the antibody positivity cut-off, indicating the limit of detection. F) Hind limb bone mineral density and G) bone mineral density of bCII-immunized fore and hind limbs over time. H) Pain-like behaviour at day 47 post primary immunization. Graphs show the median [IQR], with each symbol in F-H) representing an individual mouse. For B-D), statistical analysis was performed using a mixed effects model with the Geisser-Greenhouse correction and Tukey's multiple comparisons test, with resulting p-values shown in the graphs. Kruskal-Wallis with Dunn's multiple comparisons test was used for F) and H), and the resulting p-values were p = 0.0008 and p = 0.0003 respectively, with p-values for pairwise comparisons indicated on the graphs. For G), a Spearman correlation coefficient (r) was calculated and p < 0.05 was considered significant.

Article Snippet: Male DBA/1J mice (000670; Jackson Laboratories; USA) were co-housed at the conventional facility at Western University according to the Canadian Council on Animal Care guidelines.

Techniques: Micro-CT, Injection

Journal: Journal of Translational Autoimmunity

Article Title: T cell proliferative response to a homocitrullinated peptide correlates with joint pathology in collagen induced arthritis

doi: 10.1016/j.jtauto.2025.100345

Figure Lengend Snippet: Collagen Induced Arthritis Histopathology in DBA/1J Metatarsophalangeal Joints. Representative A) hematoxylin + eosin and B) toluidine blue micrographs of joints from DBA/1J mice immunized with bovine type II collagen (arthritic: N = 9; non-arthritic: N = 11), or PBS (N = 14). The first image in each row was obtained at 140× magnification (scale bar = 300 μm). Adjacent images show enlargement of the outlined regions, obtained at 400× magnification (scale bar = 100 μm). Histopathological features: pannus (yellow arrowheads) with bone marrow penetration (green asterisk), joint debris (green arrows), synovitis (black asterisk), proteoglycan loss (yellow oval), and cartilage erosion (red arrowheads). C) Four histopathology parameters, synovial inflammation, bone erosion, proteoglycan loss, and cartilage erosion, were each scored out of 3. Graphs show the median [IQR], with each symbol representing an individual mouse. Statistical analysis was performed using Kruskal-Wallis with Dunn's multiple comparisons test, and the resulting p-values were p = 0.0013, p = 0.0003, p = 0.0016, and p = 0.0003 respectively, with p-values for pairwise comparisons indicated on the graphs.

Article Snippet: Male DBA/1J mice (000670; Jackson Laboratories; USA) were co-housed at the conventional facility at Western University according to the Canadian Council on Animal Care guidelines.

Techniques: Histopathology

Journal: Journal of Translational Autoimmunity

Article Title: T cell proliferative response to a homocitrullinated peptide correlates with joint pathology in collagen induced arthritis

doi: 10.1016/j.jtauto.2025.100345

Figure Lengend Snippet: Citrullinated and Homocitrullinated Proteins/Peptides are Present in DBA/1J Metatarsophalangeal Joints. A) Representative hematoxylin + eosin (H&E) at 80× magnification and immunofluorescent micrographs at 20× magnification of joints from DBA/1J mice immunized with bovine type II collagen (arthritic: N = 9; non-arthritic: N = 10) or PBS (N = 9). Scale bars represent 500 μm. Max projections of Z-stacks show nuclei (DAPI; blue), citrullinated proteins/peptides (CitP; green), and homocitrullinated proteins/peptides (HomoCitP; red). Corrected total fluorescence intensity for B) CitP and C) HomoCitP in three joint structures: bone marrow, synovium, and cartilage. Graphs show the median [IQR], with each symbol representing an individual mouse. Statistical analysis was performed using Kruskal-Wallis with Dunn's multiple comparisons test, and the resulting p-values were p = 0.0046, p = 0.0084, p = 0.4076, p = 0.0143, p = 0.0136, and p = 0.1733 respectively, with p-values for pairwise comparisons indicated on the graphs. ns: not significant.

Article Snippet: Male DBA/1J mice (000670; Jackson Laboratories; USA) were co-housed at the conventional facility at Western University according to the Canadian Council on Animal Care guidelines.

Techniques: Fluorescence

Journal: Journal of Translational Autoimmunity

Article Title: T cell proliferative response to a homocitrullinated peptide correlates with joint pathology in collagen induced arthritis

doi: 10.1016/j.jtauto.2025.100345

Figure Lengend Snippet: Splenic T Cell Proliferation Following Stimulation with Type II Collagen Protein. Splenocytes isolated at day 49 post primary immunization from DBA/1J mice immunized with bovine type II collagen (bCII) (arthritic: N = 8; non-arthritic: N = 7) or PBS (N = 10) were cultured in media alone or 80 μg/mL bCII protein. Following 72 h incubation, A) CD4 + and B) CD8 + T cell proliferation following stimulation with bCII was measured by flow cytometry and is shown as a mean (±SD) stimulation index, with data points representing individual mice. Stimulation indices greater than 1.6 (dashed line) were considered a positive response. Statistical analysis was performed using one-way ANOVA with Tukey's multiple comparisons test, and the resulting p-values were p = 0.0054 and p = 0.0987 respectively, with p-values for pairwise comparisons indicated on the graphs. ns: not significant.

Article Snippet: Male DBA/1J mice (000670; Jackson Laboratories; USA) were co-housed at the conventional facility at Western University according to the Canadian Council on Animal Care guidelines.

Techniques: Isolation, Cell Culture, Incubation, Flow Cytometry

Journal: Journal of Translational Autoimmunity

Article Title: T cell proliferative response to a homocitrullinated peptide correlates with joint pathology in collagen induced arthritis

doi: 10.1016/j.jtauto.2025.100345

Figure Lengend Snippet: Splenic T Cell Proliferation Following Stimulation with Citrullinated and Homocitrullinated Peptides . Splenocytes isolated at day 49 post primary immunization from DBA/1J mice immunized with bovine type II collagen (arthritic: N = 8; non-arthritic N = 7), or PBS (N = 10) were cultured in media alone, 100 μg/mL citrullinated peptide (CitP), or 100 μg/mL homocitrullinated peptide (HomoCitP). Following 72 h incubation, CD4 + and CD8 + T cell proliferation following stimulation with A-B) CitP and C-D) HomoCitP was measured by flow cytometry and is shown as a mean (±SD) stimulation index, with data points representing individual mice. Stimulation indices greater than 1.6 (dashed line) were considered a positive response. Statistical analysis was performed using one-way ANOVA with Tukey's multiple comparisons test, and the resulting p-values were p = 0.5857, p = 0.3012, p = 0.0036, and p = 0.0024 respectively, with p-values for pairwise comparisons indicated on the graphs. ns: not significant.

Article Snippet: Male DBA/1J mice (000670; Jackson Laboratories; USA) were co-housed at the conventional facility at Western University according to the Canadian Council on Animal Care guidelines.

Techniques: Isolation, Cell Culture, Incubation, Flow Cytometry

Journal: Journal of Translational Autoimmunity

Article Title: T cell proliferative response to a homocitrullinated peptide correlates with joint pathology in collagen induced arthritis

doi: 10.1016/j.jtauto.2025.100345

Figure Lengend Snippet: RA-Specific Serum IgG Antibodies in DBA/1J Mice. Sera were collected biweekly from DBA/1J mice immunized with bovine type II collagen (bCII) (arthritic: N = 9–18; non-arthritic: N = 17–37), or PBS (N = 14) and tested via indirect ELISA for A) anti-CitP, and B) anti-HomoCitP IgG antibodies. Graphs show the median [IQR] for each group, with a cut-off indicating the limit of detection (dashed line). Statistical analysis was performed using a mixed effects model with the Geisser-Greenhouse correction and Tukey's multiple comparisons test. The resulting p-values are indicated on the graphs.

Article Snippet: Male DBA/1J mice (000670; Jackson Laboratories; USA) were co-housed at the conventional facility at Western University according to the Canadian Council on Animal Care guidelines.

Techniques: Indirect ELISA

Journal: Cancer Discovery

Article Title: A Covalent Allosteric Molecular Glue Suppresses NRF2-Dependent Cancer Growth

doi: 10.1158/2159-8290.CD-25-1187

Figure Lengend Snippet: VVD-065 exhibits strong antitumor effects in syngeneic settings. A and B, Antitumor efficacy of VVD-065 in the KLN-205 syngeneic orthotopic model. KLN-205 cells were injected into the tail vein of DBA/2 animals and then dosed with vehicle or VVD-065 50 mg/kg once a day (QD). A, Representative hematoxylin and eosin images of lungs from non-tumor bearing animals, vehicle-treated animals, and VVD-065–treated animals. B, Kaplan–Meier survival analysis comparing VVD-065 with vehicle ( n = 30 animals/group). Statistical significance was calculated by the Gehan–Breslow–Wilcoxon test (****, P < 0.0001). C, Antitumor efficacy of VVD-065 in the KLN-205 syngeneic heterotopic model. Data are shown as mean ± SEM; n = 10 animals/group. Mice were dosed orally with VVD-065 at indicated doses. Statistical significance was calculated by two-way ANOVA (****, P ≤ 0.0001). OS, overall survival.

Article Snippet: KLN-205 cells were harvested in the exponential growth phase and suspended in 100 μL PBS to deliver 0.5 × 10 6 cells via a tail vein injection in DBA/2 mice (The Jackson Laboratory).

Techniques: Injection