Biology of IL‐38 and its role in disease

Summary IL ‐38 belongs to the IL ‐36 cytokines, which in turn are part of the IL ‐1 family. The first biological function of IL ‐38 described was blocking the activation of the IL ‐36R signaling similar to IL ‐36Ra. Since IL ‐36 cytokines require processing in order to become fully active, it is likely that IL ‐38 also must be processed to become maximally active. However, the protease(s) responsible for this is currently not known. In addition of IL ‐38 binding IL ‐36R, it has been proposed it can also interact with the co‐receptor TIGIRR 2. IL ‐38 is expressed in several tissues including tonsils, placenta, heart and brain, and IL ‐38 has been implicated in a wide variety of diseases including cardiovascular and autoimmune disease. Here, we discuss the discovery and biological function of IL ‐38, and its role in the pathogenesis of a wide variety of diseases.