IL-37/IL-18Rα complex: receptors, signaling and pathogenesis of diseases

Print Friendly, PDF & Email

AJBM  Volume 2, Issue 1, pages 48–56, January 2014

Christopher Schultz,  Andrew Morin, David B. Greig 


The interleukin 1 (IL-1) family, a subset of cytokines consisting of IL-1a and IL-1b, in addition, seven novel IL-1 family members have been identified based on their sequence homology, three-dimensional protein structure, gene location and receptor binding profile. These proteins are now termed IL-36Ra, IL-36a, IL-36b, IL-36g, IL-37, IL-38 and IL-33 (previously known as IL-1F5, IL-1F6, IL-1F8, IL-1F9, IL-1F7, IL-1F10 and IL-1F11, respectively). Its plays crucial roles in host defense mechanism and in the development of inflammatory diseases. Although IL-17A is the signature cytokine produced by T helper 17 (Th17) cells, IL-17A and other IL-17 family cytokines have multiple sources ranging from immune cells to non-immune cells. The IL-17 family signals via their correspondent receptors and activates downstream pathways that include NFκB, MAPKs and C/EBPs to induce the expression of anti-microbial peptides, cytokines and chemokines. The proximal adaptor Act1 is a common mediator during the signaling of all IL-17 cytokines so far and is thus involved in IL-17 mediated host defense and IL-17-driven autoimmune conditions. This review will give an overview and recent updates on the IL-37/IL-18Rα complex, the activation and regulation of IL-37 signaling as well as diseases associated with this cytokine family.

Key word: IL-37, MAPKs, C/EBPs, IL-17, IL-18Rα