IL-17E/IL-25: Proteins and Enzymes

IL-17E/IL-25 (Interleukin-25) is a cytokine that promotes Th2-biased immune responses. This is in contrast to other IL-17 family members which promote Th1- and Th17-biased inflammation. IL-25 is an important mediator of allergic reactions and protection against intestinal parasites. During helminth infections and allergic reactions, IL-25 is locally upregulated in intestinal and airway epithelial cells, atopic dermatitis skin lesions, and local Th2 cells, eosinophils, and basophils. It binds to IL-17 RB but also requires IL-17 RA to exert its activity. IL-25 acts on a variety of cell types which respond with increased production of Th2 cytokines (e.g. IL-4, IL-5, IL-13) and reduced production of Th1 and Th17 cytokines (e.g. IFN-gamma, IL-12, IL-23, IL-17A, IL-17F). Airway IL-25 can be activated by MMP-7, a protease that is upregulated in airway epithelium in response to allergen exposure. Cleaved IL-25 shows enhanced binding to IL-17 RB and stronger induction of Th2 cytokines. IL-25 also promotes vascular endothelial cell proliferation and assembly into tubular structures. It supports the integrity of the blood-brain barrier and limits CD4+ T cell infiltration into the brain.