(A) Heatmaps of differentially expressed genes in activated CD8+ T cells treated with the indicated IL-10 variants for 24 hours, analyzed by RNA-seq (n=2 biological replicates). (B) Fold change of select IL-10-regulated genes in activated CD8+ T cells treated with the indicated IL-10 variants for 24 hours, analyzed by RNA-seq (n=2 biological replicates). (C) Levels of IFN-γ, IL-9, and granzyme B from activated human CD8+ T cells cultured with the indicated IL-10 variants, measured by ELISA. (mean ± SEM, n=3, N=3, ns P>0.05, *P<0.05, **P<0.01, two-sided Student’s t test). (D) Levels of IFN-γ from isolated CD4+ T cells polarized to Th1 cells in the presence or absence of the indicated IL-10 variant for 5 days, measured by ELISA (mean ± SEM, n=3, N=2 *P<0.05. **P<0.01, two-sided Student’s t test). (E) Schematic depicting myeloid-biased IL-10 agonists decoupling the pro- and anti-inflammatory functions of IL-10.