IL-13 uses the IL-4 receptor type II (IL-4RII), a complex formed by an IL-4Rα chain and an IL-13Rα1 chain. Initially, the ligand (IL-4 or IL-13) binds to the IL-4Rα chain and IL-13Rα1 respectively; thereafter, a secondary chain (IL-13Rα1 and IL-4Rα respectively) will also bind, forming the complete IL-4RII. The IL-4/IL-4Rα complex, however, can also bind to a different secondary chain, the IL-2Rγc, forming the IL-4 receptor type I (IL-4RI). In non-hematopoietic cells, IL-2Rγc is poorly expressed; on the other hand, IL-13Rα1 is poorly expressed in lymphocytes but abundantly in all non-hematopoietic cells; myeloid cells express both of them to a certain degree. This different distribution of secondary chains accounts for the difference in distribution of completed receptors, with being IL-4RI prevalently expressed in lymphocyte, and IL-4RII prevalently in non-hematopoietic cells. Consequently, only IL-4, through IL-4R1, is able to modulate the function of lymphocytes inducing Th2 polarisation and B cells IgG1/IgE class switching, while IL-13 is mainly acting on myeloid cells and non-hematopoietic cells, having strong effects on mucus production, smooth muscle contraction, epithelium permeabilisation (e.g. allergic asthma).
