IL-33/ST2 Pathway as a Rational Therapeutic Target for CNS Diseases

Interleukin (IL)-33 is a member of the interleukin-1 cytokine family that is produced by many different types of tissues including the central nervous system (CNS). IL-33 mediates its effects via its heterodimeric receptor complex, comprised of ST2 and the IL-1 receptor accessory protein (IL-1RAcp). As a pleiotropic nuclear cytokine, IL-33 is a crucial factor in the development of cardiovascular diseases, allergic diseases, infectious diseases, and autoimmune diseases. Recently, accumulated evidence shows that the IL-33/ST2 axis plays a crucial and diverse role in the pathogenesis of CNS diseases, including neurodegenerative diseases, cerebrovascular diseases, infectious diseases, traumatic CNS injury, chronic pain, etc. In this review, we discuss the recent findings in the cellular signaling of IL-33 and advancement of the role of IL-33 in several CNS diseases, as well as its therapeutic potential for the treatment of those diseases.