Fig 2: LINC00240 is downregulated in placenta samples of preeclampsia patients. A qPCR measurement on LINC00240 levels in placenta tissues from preeclampsia patients (n = 24) and normal pregnant women (n = 24). B qPCR measurement on CK7 levels in placenta tissues from preeclampsia patients (n = 24) and normal pregnant women (n = 24). C qPCR measurement on Arg-1 and iNOS levels in placenta tissues from preeclampsia patients (n = 24) and normal pregnant women (n = 24). D A correlation analysis between Arg-1, iNOS, and LINC00240 levels in placenta tissues from preeclampsia patients (n = 24). *P < 0.05 and **P < 0.01

Fig 3: TNF inhibits M2 gene expression (related to Fig 1).(A) Gating strategy of wild-type BMDMs stained for Arg1, RELMa, and CD301. (B) Representative blots of wild-type BMDMs stimulated with IL4/IL13 or IL4/IL13 + TNF and percentages of RELMa+ and CD301+ macrophages were determined by flow cytometry analysis. (C) Wild-type BMDMs were stimulated with IL4/IL13, IL4/IL13 + TNF, or left untreated and percentages of CD301+ of F4/80+ macrophages were determined by flow cytometry analysis. (D) Representative blots for Fig 1D. (E) Wild-type BMDMs were stimulated with IL4/IL13, IL4/IL13 + TNF, and/or Etanercept and percentages of Arg1+ of F4/80+ macrophages were determined by flow cytometry analysis. Data represent three independent experiments. (F) Gating strategy for the sorting of wound macrophages. Representative flow cytometry analysis of single cell suspensions isolated from Balb/c wild-type wound tissue at 14 dpi. 7-AAD- single cells were gated and analyzed for expression of CD45 and CD11b. 7-AAD-CD45+CD11b+ cells were gated and analyzed for expression of CD11b and F4/80. 7-AAD-CD45+CD11b+F4/80+ cells were sorted by flow cytometry. (G) Gating strategy of small peritoneal macrophages from solvent or Etanercept-treated mice stained for Arg1 and RELMa. All values are means ± SEM; *P < 0.05; ****P < 0.0001. Statistically significant differences were determined by one-way ANOVA with Tukey correction. If not indicated otherwise superscripts show statistical significance compared with the control group. n = 3 biological replicates.

Fig 4: Arg1 expression is controlled by IL6.(A) Wild-type (WT) BMDMs were stimulated with LPS and treated with the JAK2 inhibitor AG 490 or both. Data shown are representative of three experiments. (B) Wild-type, Il6-/-, and Myd88-/- BMDMs were stimulated with LPS for 24 or 48 hours. CM of LPS, 48-hour–stimulated BMDMs of all genotypes, were transferred to naïve wild-type and Il6-/- and Myd88-/- BMDMs for further 24 hours. (C) Wild-type and Il6r-/- BMDMs were stimulated with LPS for 48 hours. CM were transferred to naïve wild-type and Il6r-/- BMDMs. (D) Whole-cell lysates of wild-type BMDMs, which were left untreated (Ctrl) or treated with LPS or lactate + IL6, were analyzed by Western blotting. (E) Heatmaps showing transcriptomic data from profile GSE115354 and RNA-seq analysis of Ctrl and IL4/IL13-stimulated BMDMs. (F) Wild-type and Nos2-/- BMDMs were left untreated or stimulated with LPS or IL4/IL13. CM of both genotypes were transferred to untreated wild-type and Nos2-/- BMDMs. (G) Concentration of IL6 in the supernatant of wild-type and Nos2-/- BMDMs stimulated with LPS was measured by enzyme-linked immunosorbent assay (ELISA). n = 3 biological replicates. Statistically significant differences were determined by a two-way ANOVA with Tukey correction; * displays that increased cell death was observed and therefore loading control (Grb2) was decreased. All values are means ± SEM; ****P < 0.0001. If not indicated otherwise, superscripts show statistical significance compared to the control group.

Fig 5: Type 1 IFNs and cell death suppression are inversely associated with histone lactylation.(A) Wild-type BMDMs were treated with LPS for 48 hours, and live/dead staining was used. Cells were sorted for viable cells and late apototic cells (ACs). (B) Wild-type and Nos2-/- BMDMs were left untreated (Ctrl) or were stimulated with LPS, and cell death was assayed by LDH release. (C) Wild-type BMDMs were left untreated or were stimulated with LPS, and where indicated, the ferroptosis inducer RSL3 was added. Cell death was detected via CellTox green cytotoxicity assay. (D) Wild-type BMDMs differentiated with macrophage colony-stimulating factor (M-CSF) or LCCM were stimulated with LPS, and the percentages of Arg1+ of F4/80+ macrophages were determined. (E) The concentration of IL6 in the supernatant was measured by ELISA. (F) Wild-type BMDMs were differentiated with M-CSF or LCCM and stimulated with LPS. LDH release was evaluated over time. (G) Overview of LPS-induced cell death pathways. Wild-type, Asc-/-, and Trif-/- BMDMs (H) or Ifnar-/- BMDMs (I) were stimulated with LPS, and LDH release was evaluated. (J) Ifnar-/-, Nos2-/-, and wild-type BMDMs, differentiated with LCCM or CSF, were left untreated or were stimulated with LPS. * displays that increased cell death was observed. All values are means ± SEM; *P < 0.05; **P < 0.01; ****P < 0.0001. Statistically significant differences were determined by a one-way (A, E, G, and H) or two-way (B to D) ANOVA with Bonferroni correction; n = 3 biological replicates. n.s., not significant.