Fig. 3: IL-6 and G-CSF drive emergency myelopoiesis and production of MS1 monocytes.
a EM scores (left) and IL1R2 expression (right) in patients from the PBO arm of COVACTA grouped by mechanical ventilation status on day 28. Boxes show the median and interquartile range (IQR) for each patient cohort, with whiskers extending to 1.5 IQR in either direction from the top or bottom quartile. p values shown are calculated for each comparison using a two-tailed Wilcoxon rank-sum test. b EM scores over time in patients from the PBO or TCZ arm of COVACTA, grouped by mechanical ventilation status. EM scores are averaged across all patients for each group and timepoint. Error bars indicate the 95% confidence interval of the mean. Asterisks indicate a false discovery rate (FDR) < 0.05, computed by comparing the PBO and TCZ group at each timepoint (two-tailed Wilcoxon rank sum test, corrected for multiple testing). c Volcano plot showing the Pearson correlation between changes in protein levels and changes in EM score from baseline to day 3 in the TCZ group. Significance of each correlation was calculated with a two-sided permutation test. Proteins with FDR of <0.01 are highlighted in red. d G-CSF levels over time in patients from the PBO or TCZ arm of COVACTA, grouped by mechanical ventilation status. G-CSF levels are averaged across all patients for each group and time point. Error bars indicate the 95% confidence interval of the mean. Asterisks indicate a false discovery rate (FDR) < 0.05, computed by comparing the PBO and TCZ group at each timepoint (two-tailed Wilcoxon rank sum test, corrected for multiple testing). e Fraction of MS1 (IL1R2 + HLA-DRlow) among monocytes in HSPCs incubated with each cytokine at the indicated concentration (n = 3 replicates for each cytokine and concentration). f Flow cytometry density plot of CD14+ monocytes from HSPCs treated with healthy serum (HS) or healthy serum with 10 ng/mL IL-6 and G-CSF (HS + G6) (representative across 3 experiments). g Violin plot of MS1 gene program usage in monocytes differentiated from HSPCs treated with HS or HS + G6. h Gene weight correlation between the MS1 program detected in patients (x-axis) and the MS1 program detected in differentiated HSPCs (y-axis). Significance of the Pearson correlations (r) was calculated with a permutation test. The top 20 genes with the highest z-score loadings in the patient MS1 program are labeled. NPX normalized protein expression.
