Fig. 7.

Serine metabolism deficiency orchestrates macrophage polarization and JAK–STAT1 signaling via IGF1-dependent p38 activation. Igf1^fl/flLyz2-Cre⁻ (IGF1R-WT) and Igf1R^fl/flLyz2-Cre⁺ mouse (IGF1R-KO) BMDMs were stimulated with IFN-γ for 12 h or IL-4 for 24 h, followed by qRT‒PCR analysis of M1 (a) and M2 (b) marker expression. IGF1R-WT and IGF1R-KO BMDMs were treated with IFN-γ (c) or IL-4 (d) for the indicated times, followed by western blot analysis with the indicated antibodies. PHGDH-WT and PHGDH-KO BMDMs were transfected with siControl or siIGF1R and were then stimulated either with IFN-γ for 12 h (e, f) or the indicated times (i) or with IL-4 for 24 h (g, h) or the indicated times (j), followed by qRT‒PCR or western blot analysis. WT BMDMs transfected with siControl or siIGF1R were starved of SG, supplemented with or without 400 μM SAM, and then stimulated either with IFN-γ for 12 h (k) or 30 min (m) or with IL-4 for 24 h (l) or 30 min (n), followed by qRT‒PCR or western blot analysis. The data are from three independent experiments with biological duplicates in each and are shown as the mean ± SEM values (n = 3) (a, b, e, g, k, l) or are representative of three independent experiments (c, d, f, h, i, j, m, n). *p < 0.05, **p < 0.01, ***p < 0.001