IL26

Interleukin-26 (IL-26), also designated AK155 or IL-26, is a pro-inflammatory cytokine belonging to the IL-10 family. It is predominantly secreted by Th17 cells, γδ T cells, and activated macrophages, mediating immune responses through a heterodimeric receptor complex comprising IL-10R2 and IL-20R1. Mechanistically, IL-26 binds to extracellular DNA in inflammatory microenvironments, amplifying JAK-STAT and NF-κB signaling pathways to drive neutrophil recruitment and epithelial cell activation. This cytokine is implicated in chronic inflammatory disorders, particularly psoriasis, rheumatoid arthritis, and inflammatory bowel disease, where dysregulated IL-26 expression correlates with tissue damage and disease progression.
Current therapeutic strategies targeting IL-26 focus on neutralizing antibodies and receptor antagonists. Preclinical studies demonstrate that IL-26 blockade attenuates pathological inflammation in psoriasis models by suppressing Th17-mediated responses. Clinical-stage inhibitors like ALX-018 (a trivalent Nanobody) have shown promise in phase I trials for autoimmune conditions. However, challenges persist in balancing efficacy with potential immunosuppressive risks, necessitating further mechanistic exploration of IL-26's dual role in microbial defense versus autoimmunity.