Fig. 5: The anti-inflammatory role of TREX1 in AIA rats.
From: Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis
A Hind paw volumes and arthritis scores in AIA rats with AAV-mediated TREX1 overexpression. Healthy control and AIA rats were treated with vehicle control, the positive control drug (7.6 mg/kg/week MTX), AAV-TREX1 (1 × 1011 or 1 × 109 PFU) by tail vein injection 10 days before AIA induction or with AAV-TREX1 (2.5 × 1010 or 2.5 × 108 PFU) by joint injection 10 days before AIA induction. Arthritis scores and hind paw volumes were measured every 3 days. All the samples are biologically independent, and statistical significance was calculated by one-way ANOVA, **p < 0.01 versus the AIA group, #p < 0.05, ##p < 0.01 for the AIA group compared with the healthy control group. Data are presented as the mean ± s.e.m. (n = 6 in all groups). B Changes in the cfDNA concentration in the serum of AIA rats with AAV-mediated TREX1 overexpression. On Day 30, the amount of cfDNA in serum from all treatment groups was measured. The amount of cfDNA in each treatment group was quantified as well. All samples are biologically independent, and statistical significance was calculated by one-way ANOVA, **p < 0.01 versus the AIA group. Data are presented as the mean ± s.e.m. (All groups n = 6). C 3D Micro-CT images of damaged swollen joints’bone were reconstructed using Inveon Research Workplace with a resolution of 19 μm. Various degrees of bone destruction are shown in the red box with enlarged images. The yellow arrows indicate the region of bone destruction. D Immunomodulatory effect of TREX1 in AIA rats. For immunological analysis, blood lymphocytes were harvested from these animals for flow cytometric analysis of T-cell activation using fluorescent antibodies against CD45, CD3, CD4, CD8, and Foxp3. Representative flow charts for the purification of CD8+ cells gated on CD3+ T lymphocytes and Foxp3 cells gated on CD4+ T lymphocytes from Peyer’s patches (PPs). The quantitative bar charts show the percentage of CD8+ T cells among CD3+ T cells and the percentage of Foxp3+ Treg cells among CD4+ T cells. All samples are biologically independent, and statistical significance was calculated by one-way ANOVA, *p < 0.05, **p < 0.01 versus the AIA group. Data are presented as the mean ± s.e.m. (All groups n = 6).
