Biology of IL-36 cytokines and their role in disease

IL-36 alpha, IL-36 beta, IL-36 gamma, and IL-36Ra, collectively called IL-36 cytokines, are part of the IL-1 family. IL-36 alpha, IL-36 beta, and IL-36 gamma are IL-36 receptor (IL-36R) agonists, while IL-36Ra is a receptor antagonist that blocks the activation of IL-36R signaling. IL-36 cytokines require processing in order to become fully active, however the protease(s) responsible for this are currently not known. The IL-36 receptor pathway activates dendritic cells and plays a role in polarizing T-helper responses. The skin is the predominant site where IL-36 cytokines are expressed and several reports have established that they play a significant role in the pathogenesis of skin diseases. In this review the discovery and biological function of the cytokines IL-36 alpha, IL-36 beta, IL-36 gamma and IL-36Ra will be discussed, and their role in the pathogenesis of a wide variety of diseases. (C) 2013 Elsevier Ltd. All rights reserved