Extended Data Fig. 8: Characterization and modeling of biased type I IL-4 receptor signaling elicited by hNeo-4.
From: Design of cell-type-specific hyperstable IL-4 mimetics via modular de novo scaffolds
a-b, STAT6 phosphorylation induced by hIL-4, hNeo-4, and super-4 in (a) Ramos B cells and (b) A549 lung epithelial cells. Data represent mean ± SD (n = 3 biologically independent samples). c, Heat map showing the induction levels of the top 30 differentially expressed genes (DEGs) in IL-4-treated fibroblasts. d-e, Prediction accuracies for STAT6 activation induced by mNeo-4 or mIL-4 in A20 B cells, primary bone marrow-derived macrophages (BMDMs), and 3T3 fibroblast cells, using either the (d) sequential or (e) multivalent IL-4 signaling model. f, Cross-validation of the accuracies of the multivalent model STAT6 activation predictions in human Ramos B cells, primary monocytes, primary monocyte-derived macrophages (MDMs), primary fibroblasts, and A549 lung epithelial cells. g, Fitted equilibrium dissociation constants (KD) of hIL-4, hIL-13, or hNeo-4 binding to IL-4 receptor chains obtained from the multivalent model. N.B. indicates no binding. h, Fitted KD values of mIL-4 or mNeo-4 binding to IL-4 receptor chains obtained from the multivalent model. i, Experimental STAT6 activation by hIL-4, hIL-13, or hNeo4 compared to multivalent model predictions in MDMs, primary fibroblasts, and A549 cells.
