Fig. 3: IL-10→IL-2 adaptors convert IL-10 stimulation into IL-2 signaling.
a Model comparing natural IL-10 signaling through IL-10Rα and IL-10Rβ (left, PDB ID: 6X93) vs. signaling through IL-10→IL-2 cytokine adaptors (right) which dimerize IL-2Rβ and γc. Adaptors are modeled using structures of IL-10 and scFv 9D7 (PDB ID: 1LK3) overlaid with IL-10 and IL-10Rα (PDB ID: 6X93), IL-2RβNb6 bound to IL-2Rβ (PDB ID: 7S2S) and γcNb6 bound to γc (PDB ID: 7S2R). b Cartoon representations of adaptors 10.1, 10.2, 10.3, and 10.4. c IL-10→IL-2 adaptors induce dose-dependent pSTAT5 signal similar to IL-2. Dose–response curves are shown for pSTAT5 in YT-1 cell line stimulated for 20 min with human IL-2 or IL-10 with equimolar Adaptor 10.1 and 10.2 or Adaptor 10.3 and 10.4. Data are plotted as mean, n = 2, N = 3. d Normalized pSTAT5 response in YT-1 cells stimulated with the indicated cytokines or adaptors, normalized as a percentage of maximum IL-2 pSTAT5. Data are plotted as mean, n = 2. e Adaptors 10.1 and 10.2 suppress IL-10-induced pSTAT3 and promote IL-2 like pSTAT5 signaling. Dose–response curves for pSTAT5 and pSTAT3 are shown in human CD4+ T cell blasts stimulated with 10 nM IL-10 and increasing concentrations of equimolar Adaptor 10.1 and 10.2. n = 2 replicates per condition. Source data are provided as a Source data file.
