Interleukin 17 - Gene Expression

Gene Expression

The gene for human IL-17 is 1874 base pairs long and was cloned from CD4+ T cells. Each member of the IL-17 family has a distinct pattern of cellular expression. The expression of IL-17A and IL-17F appear to be restricted to a small group of activated T cells, and upregulated during inflammation. IL-17B is expressed in several peripheral tissues and immune tissues. IL-17C is also highly upregulated in inflammatory conditions, although in resting conditions is low in abundance. IL-17D is highly expressed in the nervous system and in skeletal muscle and IL-17E is found at low levels in various peripheral tissues.

Much progress has been made in the understanding of the regulation of IL-17. At first, Aggarwal et al. showed that production of IL-17 was dependent on IL-23. Later, a Korean group discovered that STAT3 and NF-κB signalling pathways are required for this IL-23-mediated IL-17 production. Consistent with this finding, Chen et al. showed that another molecule, SOCS3, plays an important role in IL-17 production. In the absence of SOCS3, IL-23-induced STAT3 phosphorylation is enhanced, and phosphorylated STAT3 binds to the promotor regions of both IL-17A and IL-17F increasing their gene activity. In contrast, some scientists believe IL-17 induction is independent of IL-23. Several groups have identified ways to induce IL-17 production both in vitro and in vivo by distinct cytokines, called TGF-β and IL-6, without the need for IL-23. Although IL-23 is not required for IL-17 expression in this situation, IL-23 may play a role in promoting survival and/or proliferation of the IL-17 producing T-cells. Recently, Ivanov et al. found that the thymus specific nuclear receptor, ROR-γ, directs differentiation of IL-17-producing T cells.