Interleukin-4 receptor signaling pathways in asthma pathogenesis

Asthma is a chronic allergic inflammatory disease, the initiation and progression of which is dependent on the cytokines interleukin (IL)-4 and IL-13 acting through related receptor complexes. Disease pathogenesis is effected by intracellular signaling pathways that couple primarily to specific motifs within the intracellular domain of the IL-4 receptor alpha chain (IL-4Ralpha), a subunit that is common to the IL-4 and IL-13 receptor complexes. Recent studies using genetic approaches have identified distinct functions for the respective IL-4Ralpha-coupled signaling pathways in regulating both early and chronic stages of asthma. Polymorphisms in components of the IL-4 and IL-13 cytokine-receptor axes are associated with allergy and asthma, suggesting that variations among individuals in the activity of this pathway contribute to disease susceptibility and manifestations.