Genetic deletion of neutrophil-specific PD-L1 in vivo decreases proinflammatory plasma cytokine expression, thus limiting lung injury and neutrophil infiltration in the lung and decreasing mortality. (A-C) Plasma concentration of TNF-α (A), IL-6 (B), and IL-10 (C) were determined by enzyme-linked immunosorbent assay. Plasma concentrations of TNF-α and IL-6 were significantly reduced in PD-L1^flox/flox CLP mice when compared with levels in PD-L1^WT/WT CLP mice, but were still higher than in sham-treated PD-L1^WT/WT mice or sham-treated PD-L1^flox/flox mice. IL-10 concentration was significantly elevated in PD-L1^flox/flox CLP mice when compared with PD-L1^WT/WT CLP mice (n = 6). *P < .05, 1-way analysis of variance [ANOVA]. (D) Lung injury score and the representative histopathological images of the lungs. PD-L1^flox/flox CLP mice demonstrate significantly lower lung injury score when compared with PD-L1^WT/WT sham-treated mice, PD-L1^flox/flox sham-treated mice, and PD-L1^WT/WT CLP mice (scale bar, 100 μm) (n = 5). *P < .05, Kruskal-Wallis test with Dunn’s multiple comparisons test. (E) Representative immunofluorescence images of MPO (green) staining with blue 4′,6-diamidino-2-phenylindole (DAPI) nuclear stain in lung tissue. The percentage of MPO⁺ cells was significantly lower in PD-L1^flox/flox CLP mice when compared with that in PD-L1^WT/WT CLP mice, but was slightly higher than that in PD-L1^WT/WT mice in the sham-operation group and PD-L1^flox/flox mice (scale bar, 50 μm) (n = 5). *P < .05, 1-way ANOVA. (F) After CLP, PD-L1^flox/flox CLP mice demonstrated higher 7-day survival rates than PD-L1^WT/WT CLP mice (n = 8 for PD-L1^WT/WT and PD-L1^flox/flox mice in the sham-operation group; n = 18 for PD-L1^WT/WT and PD-L1^flox/flox CLP mice). *P < .05, by log-rank test.