The supplementary materials for the study "IRF3 activates RB to authorize cGAS-STING–induced senescence and mitigate liver fibrosis" include figures and tables that support the main findings. Supplementary Figure 1 shows that IRF3 deletion reduces cellular senescence phenotypes, including decreased cGAS-γ-H2AX co-localization, reduced SA-β-Gal staining, and reduced SASPs. Supplementary Figure 2 demonstrates that IRF3 controls senescence through the p16INK4a-RB pathway, as evidenced by reduced IFN responses and senescence markers in IRF3 KO cells. Supplementary Figure 3 shows that IRF3 interacts directly with RB, a key regulator of cellular senescence, as demonstrated by immunofluorescence and co-immunoprecipitation experiments. Supplementary Figure 4 shows that IRF3 attenuates RB hyper-phosphorylation, as shown by reduced phosphorylation of RB at T826 in cGAS KO and TBK1/IKKε double KO cells. Supplementary Figure 5 shows that IRF3 activates RB by attenuating CDK-induced RB phosphorylation, as demonstrated by reduced phosphorylation of RB at T826 in IRF3 5D-expressing cells. Supplementary Figure 6 shows that the IRF3-RB axis regulates senescence during liver fibrosis, as evidenced by reduced senescence markers and fibrosis in IRF3 KO mice. Supplementary Figures 7 and the tables provide additional data, including source data for statistics, key resource table, oligos for RT-qPCR and CRISPR, list of recombinant DNA, and MS and mRNA seq results of normal and senescent DLD1 cells.The supplementary materials for the study "IRF3 activates RB to authorize cGAS-STING–induced senescence and mitigate liver fibrosis" include figures and tables that support the main findings. Supplementary Figure 1 shows that IRF3 deletion reduces cellular senescence phenotypes, including decreased cGAS-γ-H2AX co-localization, reduced SA-β-Gal staining, and reduced SASPs. Supplementary Figure 2 demonstrates that IRF3 controls senescence through the p16INK4a-RB pathway, as evidenced by reduced IFN responses and senescence markers in IRF3 KO cells. Supplementary Figure 3 shows that IRF3 interacts directly with RB, a key regulator of cellular senescence, as demonstrated by immunofluorescence and co-immunoprecipitation experiments. Supplementary Figure 4 shows that IRF3 attenuates RB hyper-phosphorylation, as shown by reduced phosphorylation of RB at T826 in cGAS KO and TBK1/IKKε double KO cells. Supplementary Figure 5 shows that IRF3 activates RB by attenuating CDK-induced RB phosphorylation, as demonstrated by reduced phosphorylation of RB at T826 in IRF3 5D-expressing cells. Supplementary Figure 6 shows that the IRF3-RB axis regulates senescence during liver fibrosis, as evidenced by reduced senescence markers and fibrosis in IRF3 KO mice. Supplementary Figures 7 and the tables provide additional data, including source data for statistics, key resource table, oligos for RT-qPCR and CRISPR, list of recombinant DNA, and MS and mRNA seq results of normal and senescent DLD1 cells.