Cytoplasmic tail of IL-13Rα2 regulates IL-4 signal transduction

Abstract

IL (interleukin)-4 and IL-13 are key cytokines in the pathogenesis of allergic inflammatory disease. IL-4 and IL-13 share many functional properties as a result of their utilization of a common receptor complex comprising IL-13Rα1 (IL-13 receptor α-chain 1) and IL-4Rα. The second IL-13R (IL-13 receptor) has been identified, namely IL-13Rα2. This has been thought to be a decoy receptor due to its short cytoplasmic tail and its high binding affinity for IL-13 but not IL-4. IL-13Rα2 exists on the cell membrane, intracellularly and in a soluble form. Recent reports revealed that membrane IL-13Rα2 may have some signalling capabilities, and a soluble form of IL-13Rα2 can be generated in the presence of environmental allergens such as DerP. Interestingly, IL-13Rα2 has also been shown to regulate both IL-13 and IL-4 response in primary airway cells, despite the fact that IL-13Rα2 does not bind IL-4. The regulator mechanism is still unclear but the physical association of IL-13Rα2 with IL-4Rα appears to be a key regulatory step. These results suggest that the cytoplasmic tail of IL-13Rα2 may interfere with the association or activation of signalling molecules, such as JAK1 (Janus kinase 1), on IL-4Rα and thus prevents downstream signal cascade. The receptor has more complicated functions than a simple decoy receptor. In this review, we discuss newly revealed functions of IL-13Rα2.