Figure 6.

IL-36 and IL-17 secreted by multiple cell types have overlapping and non-overlapping downstream effects. IL-36 cytokines are expressed by a broad variety of cell types such as epithelial cell, fibroblast, keratinocytes, lymphocytes, monocytes, myeloid dendritic cells (DCs), monocyte-derived DCs, plasmacytoid DCs, and plasma cells. There is a feedback loop between the IL-36 and Th17 cytokines. Indeed, IL-36 cytokines are not only regulated by Th17 cytokines, but also act as activators of Th17 cells which regulate the differentiation and enhance the expression of Th17 cytokines. IL-17 is mainly secreted by IL-23-IL-17 axis, as well as other cell populations, such as CD8+ (Tc17) cells and various subsets of innate lymphocytes including γδT cells, natural killer T (NKT) cells, group 3 innate lymphoid cells (ILC3s), and ‘‘natural’’ Th17 cells. IL-36 and IL-17 signaling promote secretion of inflammatory and chemotactic molecules and immune cell infiltration and immune regulation, which closely related to many inflammatory diseases.