Fig. 6

Paquinimod ameliorates sepsis-induced immunosuppression by targeting S100a^high monocytes. a-c Mice undergoing CLP surgery were given Paquinimod [(10 mg/(kg·d)] by oral gavage for 3 d or not, followed by isolation of circulating monocytes in sham or CLP mice at 72 h post-operation. Counter plots with quantitative bar charts showed the proportion of MHC-II⁻S100A9⁺ monocytes in various groups (a). Representative confocal immunofluorescence images of S100A9⁺ monocytes in each group (Scale bar = 50 μm, 20 μm) (b). Western blotting analysis indicated the protein expression of S100A9 (c). d The survival rates of mice from disparate groups were recorded and compared within 7 d post-CLP surgery, shown by Kaplan–Meier curve. e Representative images of HE staining exhibited the pathological alterations in multiple organs of mice, including lung, liver, kidney, and heart (Scale bar = 150 μm). f-i PBMCs and plasma were collected from CLP mice treated with or without Paquinimod. Histogram and quantitative bar charts indicated the percentage of CD3⁺ cells in different groups (f). Counter plots with quantitative bar charts were compared the proportion of CD3⁺CD4⁺ cells between groups (g). Representative counter plots with quantitative bar plots showed CD3⁺CD4⁺Foxp3⁺ Tregs proportion (h). Quantitative bar plots showed and compared circulating levels of IL-2, IL-4, IL-10, IFN-γ, TGF-β and the ratio of IFN-γ to IL-4 across each group (i). Statistics were by One-way ANOVA with Tukey HSD test for comparison of two groups (a, f–i). Statistics were calculated using survival curve comparison with log-rank test (d). Data are shown as means ± SD. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, ^****P < 0.0001, One-way ANOVA, was performed in (a, f–i). CLP cecal ligation and puncture, MHC major histocompatibility complex, HE hematoxylin–eosin, PBMCs peripheral blood mononuclear cells, IL interleukins, IFN-γ interferon-γ, ANOVA analysis of variance, SD standard deviation, PAQ Paquinimod