IL-1 Family Signaling Pathway

IL-1R1 IL-1RA IL-1α IL-1β IL-18Rα IL-18Rβ IL-18 IL-18BP IL-18 ST2 IL-1RAcP IL-33R IL-33 sST2 IL-36R IL-1RAcP IL-36α IL-36β IL-36γ IL-18Rα IL-1R8 IL-37 IL-36R IL-1RAPL1 IL-38

Background

Signal transduction within the interleukin-1 (IL-1) family relies on the formation of ligand–receptor–coreceptor complexes. For example, IL-1α and IL-1β must first bind IL-1R1, which subsequently recruits the coreceptor IL-1RAcP to initiate downstream inflammatory pathways. Similar mechanisms apply to other members of the IL-1 family. Every step—from ligand production to receptor engagement—represents a potential therapeutic intervention point.

In autoimmune diseases, dysregulated activation of the IL-1 family is a major driver of chronic inflammation and tissue damage. Excessive production of pro-inflammatory mediators such as IL-1β and IL-18 leads to persistent immune stimulation, amplifying inflammation and promoting tissue destruction. Synovial injury and bone erosion in rheumatoid arthritis, as well as lesion formation in psoriasis, are closely linked to overactivation of IL-1 family members. At the same time, insufficient levels of anti-inflammatory cytokines further exacerbate the imbalance of inflammatory signaling.

Therapeutic strategies targeting the IL-1 pathway have already achieved clinical success. Biologics such as anakinra and canakinumab effectively block IL-1 signaling by competing for receptor binding or neutralizing cytokines, demonstrating robust efficacy across multiple autoimmune conditions. These advances not only provide new treatment options but also underscore the central role of the IL-1 family in autoimmune disease pathogenesis and therapy.

In summary, the IL-1 family, through its tightly regulated signaling mechanisms, plays a pivotal role in shaping immune responses. Dysregulation within this family is a key contributor to autoimmune disease development, and targeting its signaling pathways has emerged as an effective clinical strategy.