The upregulating IL-6 secreted by Tet2 −/− pMDMs activated HSCs in Tet2 ΔMye -CCl 4 mice. (A) Effect of Tet2ΔMye on serum IL-6 levels evaluated by ELISA in oil- or CCl4-treated Tet2WT and Tet2ΔMye mice (n = 4 for each group). (B) Effect of Tet2ΔMye on Il-6 mRNA levels in livers of oil- or CCl4-treated Tet2WT and Tet2ΔMye mice (n = 4 for oil-treated groups, n = 5 for CCl4-treated groups). (C) Experimental design of co-culture between Tet2+/+ or Tet2−/− HSCs and Tet2+/+ or Tet2−/− pMDMs. Tet2+/+ and Tet2−/− pMDMs were isolated from livers of CCl4-treated Tet2WT and Tet2ΔMye mice. Naïve Tet2+/+ and Tet2−/− HSCs were isolated from oil-treated Tet2WT and Tet2ΔMye mice. (D) Detection of IL-6 in the supernatant after co-culture by ELISA (n = 3 for each group). (E–G) mRNA and protein levels of Acta2 (E and G) and Col1a1 (F and G) detected by RT-PCR in Tet2+/+ and Tet2−/− HSCs co-cultured with Tet2+/+ or Tet2−/− pMDMs (n = 3 for each group). (H and I) Picrosirius red staining (H) (scale bar, 125 μm) and statistical analysis (I) of livers of oil- or CCl4-treated Tet2WT and Tet2ΔMye mice after Bindarit plus anti-IL-6 Abs treatment (n = 4 for each group). (J and K) Changes in serum ALT (J) and AST (K) levels in CCl4-treated Tet2WT and Tet2ΔMye mice after treatment with Bindarit, anti–IL-6 Abs, or Bindarit plus anti–IL-6 Abs (n = 4 for each group). Data are representative of at least two independent experiments with similar results (A–K). All data are shown as mean ± SD and were analyzed by two-way ANOVA with Sidak’s multiple comparison test (A, B, D–F, and I–K). ****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05; P > 0.05 not significant (ns). Source data are available for this figure: SourceData F8.