Act1-dependent interleukin-17 (IL-17) signaling complex (IL-17R-Act1 complex)

The Act1-dependent interleukin-17 (IL-17) signaling complex is a critical molecular assembly that mediates the pro-inflammatory effects of the IL-17 family of cytokines (Creative Proteomics, 2024; Nature Immunology, 2007). This complex primarily forms upon the binding of IL-17A or IL-17F to a heterodimeric receptor composed of IL-17 receptor A (IL-17RA) and IL-17 receptor C (IL-17RC) (NIH, 2012; Frontiers in Immunology, 2019). The key intracellular event is the recruitment of the adaptor protein Act1 (also known as TRAF3IP2 or CIKS) to the receptor's cytoplasmic SEFIR domain through homotypic interactions (Frontiers in Immunology, 2019; Nature Immunology, 2007). Once recruited, Act1 functions as a scaffold and a U-box E3 ubiquitin ligase, triggering the activation of downstream signaling pathways such as NF-kappaB, MAPK, and C/EBP (NIH, 2012; R&D Systems, 2024). These pathways drive the expression of various chemokines (e.g., CXCL1, CXCL8) and cytokines (e.g., IL-6) that promote neutrophil recruitment and tissue inflammation (Creative Proteomics, 2024; NIH, 2012). Dysregulation of this signaling complex is a hallmark of several autoimmune and chronic inflammatory conditions, including psoriasis, psoriatic arthritis, and ankylosing spondylitis (Nature Immunology, 2007; NIH, 2012). Therapeutic strategies targeting this complex include monoclonal antibodies that neutralize IL-17 ligands (e.g., secukinumab, ixekizumab) or block the IL-17RA subunit (e.g., brodalumab), thereby preventing the assembly and activation of the signaling complex (Patsnap, 2025; NIH, 2024).

Other names

IL-17 receptor complexIL-17R-Act1 complexTRAF3IP2-mediated IL-17 signaling complexCIKS-dependent IL-17 signaling complexInterleukin-17 receptor-Act1 complex

Inhibition of IL-17 cytokine binding to the receptor complex or blockade of the IL-17 receptor subunit to prevent recruitment of the Act1 adaptor protein and subsequent downstream pro-inflammatory signaling.