Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease

Abstract

Interleukin-17 (IL-17) has emerged as a central player in the mammalian immune system. Although this cytokine exerts a host-defensive role in many infectious diseases, it promotes inflammatory pathology in autoimmunity and other settings. A myriad of studies have focused on how IL-17-producing cells are generated. However, the means by which IL-17 achieves its effects, either for the benefit or the detriment of the host, are due in large part to the induction of new gene expression. Whereas many IL-17 target genes are common to different disease states, in some cases the effects of IL-17 differ depending on the target cell, infectious site or pathogen. Gene products induced by IL-17 include cytokines (IL-6, granulocyte-colony-stimulating factor, tumour necrosis factor-alpha), chemokines (CXCL1, CXCL2, CCL20, among many others), inflammatory effectors (acute-phase protesins, complement) and antimicrobial proteins (defensins, mucins). Different cell types appear to respond differently to IL-17 in terms of target gene expression, with notable differences seen in mesenchymal and epithelial cells compared with cells of haematopoietic origin. Here, we summarize the major IL-17 target genes that mediate this cytokine's activities in both autoimmune and chronic diseases as well as during various types of infections.

Figure 1

IL-17 signaling and target genes in various disease settings. In blue are representative mucosal infections where IL-17 plays a key role, along with key target genes involved in each. In pink are autoimmune diseases and the role of IL-17 and particular target genes therein.