Interleukin-17 receptor D (IL-17RD)

Interleukin‑17 receptor D is an evolutionarily conserved member of the interleukin‑17 receptor family. Originally identified as Sef due to its similar expression pattern with FGF genes, it acts primarily as a regulator rather than a classical signal-transducing cytokine receptor. IL‑17RD modulates several key cellular processes including cell proliferation, differentiation, survival, migration, invasion, and especially inflammation. It negatively regulates fibroblast growth factor signaling and also modulates other pathways such as Toll-like receptor and interleukin‑1 signaling by inhibiting NF-kB activation. Recent research has shown that IL‑17RD forms a functional complex with IL‑17RA on keratinocytes that specifically binds interleukin 17A homodimers—distinct from the canonical IL‑17RA/IL‑17RC complex—and mediates proinflammatory gene expression downstream of this cytokine. This function is particularly relevant in skin inflammation models such as psoriasis. Loss or downregulation of IL‑17RD has been associated with increased tumor formation in mice and reduced expression in various human cancers suggests it may act as a tumor suppressor; however, context-dependent pro-tumorigenic effects have also been proposed. Therapeutically relevant drugs currently target upstream ligands like interleukin 17A rather than directly binding to this specific subunit. The regulatory functions suggest that manipulation could impact both inflammatory diseases and cancer biology but would require careful consideration due to its broad immunomodulatory roles[3][5][6].

Other names

Sef (Similar expression to FGF genes)SEFIL17RD

Modulation of cytokine signaling pathways, including negative regulation of NF-kB activation and attenuation of pro-inflammatory gene expression[3]