Interleukin 17 signaling axis (IL-17 axis)

The Interleukin 17 (IL-17) signaling axis is a pivotal pro-inflammatory pathway that coordinates the immune response against extracellular pathogens and plays a central role in the pathogenesis of several autoimmune diseases [1.1.2, 1.3.1]. This axis primarily involves the Th17 cell-derived cytokines IL-17A and IL-17F, which signal through a heterodimeric receptor complex typically composed of IL-17RA and IL-17RC subunits [1.2.1, 1.4.3]. Upon ligand binding, the receptor recruits the adaptor protein Act1, initiating a signaling cascade that activates NF-κB and MAPK pathways to induce the expression of chemokines, antimicrobial peptides, and pro-inflammatory cytokines [1.2.2, 1.4.4]. While essential for host defense against bacteria and fungi, dysregulation of this axis is a major driver of chronic inflammatory conditions such as psoriasis, psoriatic arthritis, and ankylosing spondylitis [1.1.1, 1.1.5]. Therapeutic intervention in the IL-17 signaling axis has revolutionized the treatment of these conditions through the use of monoclonal antibodies [1.3.3, 1.4.1]. Drugs like secukinumab and ixekizumab target IL-17A, while bimekizumab neutralizes both IL-17A and IL-17F, and brodalumab blocks the IL-17RA receptor subunit [1.1.1, 1.3.3]. These therapies are highly effective but are associated with specific safety concerns, including an increased risk of mucocutaneous candidiasis and the potential for exacerbating inflammatory bowel disease [1.1.1, 1.3.4]. Monitoring biomarkers such as IL-17A levels and Th17 cell activity can help in assessing treatment efficacy and patient selection [1.1.4].

Other names

IL-17 pathwayTh17 signaling pathwayIL-23/IL-17 axisInterleukin-17 signaling pathway

Neutralization of IL-17 cytokines (A, F) or blockade of the IL-17 receptor (IL-17RA) to inhibit downstream pro-inflammatory signaling.