The Interleukin-17 (IL-17) family proteins, comprising six members (IL-17, IL-17B through IL-17F), are secreted, structurally related proteins that share a conserved cysteine-knot fold near the C-terminus, but have considerable sequence divergence at the N-terminus (1, 2). With the exception of IL-17B, which exists as a non‑covalently linked dimer, all IL-17 family members are disulfide-linked dimers (3). IL-17 family proteins are pro-inflammatory cytokines that induce local cytokine production and are involved in the regulation of immune functions (1, 2). Two receptors (IL-17 R, and IL-17B R), which are activated by IL-17 family members, have been identified. In addition, at least three additional orphan type I transmembrane receptors with homology to IL-17 R, including IL-17 RL (IL-17 RC), IL-17 RD, and IL‑17 RE, have also been reported (1‑4). The functions of IL-17 RC, D, and E are not known.
Human IL-17D cDNA encodes a 202 amino acid (aa) residues protein with a putative 17 aa signal peptide (5). Human and mouse IL-17D share 78% sequence identity. Among IL-17 family members, IL-17D is most closely related to IL-17B, sharing 27% aa sequence homology (5, 6). IL-17D is expressed preferentially in skeletal muscle, heart, adipose tissue, lung, pancreas, and nervous system (1, 5). Like other IL-17 family members, IL-17D modulates immune responses indirectly by stimulating the production of myeloid growth factors and chemokines including IL-6, IL-8, and GM-CSF (5). IL-17D has also been shown to suppress the proliferation of myeloid progenitors in colony formation assays. The receptor of IL-17D has not yet been identified. However, stimulation of IL-8 production by IL-17D is mediated through the activation of nuclear factor kappa-B (5). The IL-17D preparations from R&D Systems have been found to bind immobilized recombinant IL17B R/Fc in a functional ELISA.
