IL-13/IL-4 receptors and their signaling. Hematopoietic cells such as lymphocytes and dendritic cells express IL-4Rα/γC complex. IL-4, but not IL-13, binds IL-4Rα/γC and activates downstream signaling molecules JAK1/JAK3 and thenSTAT6. Activation of the IL-4‒IL-4Rα/γC‒JAK1/JAK3‒STAT6 axis induces Th2-deviated T-cell differentiation, IgE production in B cells, and the production of Th2 chemokines such as CCL17 and CCL22 from dendritic cells. On the other hand, non-hematopoietic cells such as keratinocytes express IL-4Rα/IL-13Rα1 complex. Both IL-13 and IL-4 bind IL-4Rα/IL-13Rα1 and activate downstream JAK1/TYK2/JAK2 and then STAT6/STAT3. Activation of the IL-13/IL-4‒IL-4Rα/IL-13Rα1‒JAK1/TYK2/JAK2‒STAT6/STAT3 axis down-regulates FLG, LOR and involucrin (IVL) expression, inhibits the nuclear translocation of OVO-like 1 (OVOL1), disrupts the skin barrier function, and up-regulates the production of thymic stromal lymphopoietin (TSLP), IL-25, and IL-33 in keratinocytes. Keratinocytes also express IL-13Rα2, which is a decoy receptor for IL-13. IL-13Rα2 binds IL-13 with high affinity, but does not signal.