IL-4 Receptor α Is an Important Modulator of IL-4 and IL-13 Receptor Binding: Implications for the Development of Therapeutic Targets

摘要: IL-4 is a key cytokine associated with allergy and asthma. Induction of cell signaling by involves interaction its cognate receptors, complex IL-4Ralpha either the common gamma-chain or IL-13R chain alpha1 (IL-13Ralpha1). We found that bound to extracellular domain (soluble human (sh)IL-4Ralpha) high affinity specificity. In contrast sequential mechanism binding stabilization afforded IL-13 IL-13Ralpha1, neither nor IL-13Ralpha1 contributed significantly IL-4:IL-4Ralpha complex. Based on different mechanisms IL-4R complexes, we compared effects shIL-4Ralpha an double mutein (R121D/Y124D, antagonist) IL-4- IL-13-mediated responses. Whereas antagonist blocked responses both cytokines, only IL-4. However, stabilized augmented STAT6 activation eotaxin production primary bronchial fibroblasts at suboptimal doses IL-13. These data demonstrate plays role in complexes. Under certain conditions, has potential stabilize receptor augment Thus, complete understanding interactions between their receptors may facilitate development novel treatments for asthma selectively target these cytokines without unpredicted detrimental side effects.