Ccl2/Ccl8-dependent Ccr2/Ccr3 activation drives Tet2 ^−/− monocyte recruitment and pMDMs accumulation in liver. (A) Expression of Ccr2 and Ccr3 on Tet2^+/+ and Tet2^−/− monocytes isolated from Tet2^WT and Tet2^ΔMye mice (n = 4 for each group). (B) Frequency of Ccr2⁺ and Ccr3⁺ monocytes in oil- and CCl₄-treated Tet2^WT and Tet2^ΔMye mice (n = 4 for each group). (C) Effect of anti-Ccr2/3 treatment on the frequency of pMDMs in CCl₄-treated Tet2^WT and Tet2^ΔMye (n = 4 for each group). (D and E) CD86⁺ MDMs distribution (D) and statistical analysis (E) evaluated by IF staining after anti-Ccr2/3 Ab treatment (n = 4 for each group). Blue: DAPI, red: anti-F4/80, green: anti-Ly6c, and yellow: anti-CD206. Scale bar: 400 μm. (F and G) The distribution of Inos⁺ MDMs (activated MDMs) (F) and statistical analysis (G) after anti-Ccr2/3 Ab treatment (n = 4 for each group). Blue: DAPI, red: anti-F4/80, green: anti-Ly6c, and yellow: anti-Inos. Scale bar: 400 μm. (H) Change of collagen deposition evaluated by Picrosirius red staining in livers of IgG and anti-Ccr2/3–treated Tet2^WT-CCl₄ and Tet2^ΔMye-CCl₄ mice (n = 4 for each group). (I and J) mRNA levels of Acta2 (I) and Col1a1 (J) in liver tissues of IgG and anti-Ccr2/3–treated Tet2^WT-CCl₄ and Tet2^ΔMye-CCl₄ mice (n = 4 for each group). Data are representative of at least two independent experiments with similar results (A–J). All data are shown as mean ± SD and were analyzed by two-way ANOVA with Sidak’s multiple comparison test (B, C, E, G, I, and J). ***P < 0.001; **P < 0.01; *P < 0.05; P > 0.05 not significant (ns).