The supplementary materials for the article "IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis" by Qirou Wu et al. include a comprehensive set of figures and tables that support the main findings of the study. The figures cover various aspects of the research, including: 1. **Supplementary Figure 1**: Demonstrates that IRF3 deletion attenuates cellular senescence phenotypes, as evidenced by reduced co-localization of cGAS and γ-H2AX, decreased SA-β-Gal staining, and reduced SASP production in HeLa cells and mouse fibroblasts. 2. **Supplementary Figure 2**: Shows that IRF3 controls senescence through the p16INK4a-RB pathway, with IRF3 KO cells exhibiting reduced IFN responses and senescence markers. 3. **Supplementary Figure 3**: Highlights the direct interaction between IRF3 and RB, a key regulator of cellular senescence, through immunofluorescence and co-immunoprecipitation assays. 4. **Supplementary Figure 4**:Indicates that IRF3 attenuates RB hyper-phosphorylation, which is crucial for senescence, as shown by reduced phosphorylation levels of RB and increased expression of pRB (T826) in IRF3 KO cells. 5. **Supplementary Figure 5**: Further supports the role of IRF3 in attenuating CDK-induced RB phosphorylation, with IRF3 5D mutants showing dose-dependent inhibition of RB phosphorylation. 6. **Supplementary Figure 6**: Investigates the regulation of senescence during liver fibrosis, showing that IRF3 deficiency reduces senescence markers and SASPs in BDL-induced liver fibrosis in mice. The tables provide additional data and resources, including source data for statistics, key resource table, oligos for RT-qPCR and CRISPR, lists of recombinant DNA, and mRNA sequencing results from normal and senescent DLD1 cells. These supplementary materials enhance the understanding and validation of the main findings presented in the article.The supplementary materials for the article "IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis" by Qirou Wu et al. include a comprehensive set of figures and tables that support the main findings of the study. The figures cover various aspects of the research, including: 1. **Supplementary Figure 1**: Demonstrates that IRF3 deletion attenuates cellular senescence phenotypes, as evidenced by reduced co-localization of cGAS and γ-H2AX, decreased SA-β-Gal staining, and reduced SASP production in HeLa cells and mouse fibroblasts. 2. **Supplementary Figure 2**: Shows that IRF3 controls senescence through the p16INK4a-RB pathway, with IRF3 KO cells exhibiting reduced IFN responses and senescence markers. 3. **Supplementary Figure 3**: Highlights the direct interaction between IRF3 and RB, a key regulator of cellular senescence, through immunofluorescence and co-immunoprecipitation assays. 4. **Supplementary Figure 4**:Indicates that IRF3 attenuates RB hyper-phosphorylation, which is crucial for senescence, as shown by reduced phosphorylation levels of RB and increased expression of pRB (T826) in IRF3 KO cells. 5. **Supplementary Figure 5**: Further supports the role of IRF3 in attenuating CDK-induced RB phosphorylation, with IRF3 5D mutants showing dose-dependent inhibition of RB phosphorylation. 6. **Supplementary Figure 6**: Investigates the regulation of senescence during liver fibrosis, showing that IRF3 deficiency reduces senescence markers and SASPs in BDL-induced liver fibrosis in mice. The tables provide additional data and resources, including source data for statistics, key resource table, oligos for RT-qPCR and CRISPR, lists of recombinant DNA, and mRNA sequencing results from normal and senescent DLD1 cells. These supplementary materials enhance the understanding and validation of the main findings presented in the article.