A Molecular Perspective on Th2-Promoting Cytokine Receptors in Allergic Disease

摘要

The cytokines IL-4, IL-13 and TSLP, play a key role in allergic disease by virtue of their ability to initiate, maintain, and augment Th2 responses. These molecules mediate their effects through type 1 cytokine receptors which bind cytokines with a characteristic structure. Receptors are expressed on a broad array of immune cell types, and are integral to complex cytokine networks operating in health and disease. Th2-promoting cytokines bind different configurations of receptors. Receptor subunits may exist in surface bound or soluble form, as well as in isolation or in partnership with other subunits. Sharing of receptor subunits among different cytokine receptor complexes adds to the intricate landscape. This article describes the characteristics of receptors for IL-4, IL-13 and TSLP, and their respective ligands, from a structure-function perspective. We detail the mechanisms of receptor complex assembly, the interrelated nature of these receptors, and impact on allergic inflammation. The ability for novel and atypical types of receptors to modulate inflammatory processes is also discussed. We highlight current and emerging treatments that target Th2-promoting receptor complexes. Understanding molecular features of these receptors provides insight into different disease phenotypes and the variable clinical outcomes arising from targeted therapies. These considerations can be used to inform future directions for research and creative strategies for treating individual patients.