Interleukin 39 (IL39)

Interleukin-39 (IL-39) is a recently identified cytokine belonging to the IL-12 family, primarily produced by activated B cells and monocytes. It is a heterodimeric protein composed of the Epstein-Barr virus-induced gene 3 (EBI3) subunit and the IL-23p19 subunit. Current research has begun to elucidate its significant role in mediating inflammatory and autoimmune responses. Studies, predominantly in murine models, have demonstrated that IL-39 signaling is crucial for the pathogenesis of conditions like lupus and autoimmune arthritis by promoting the differentiation and expansion of pathogenic neutrophil and Th17 cell populations. Its biological action is mediated through a receptor complex involving IL-23R and gp130, activating downstream JAK/STAT and MAPK signaling pathways. The discovery of IL-39 not only expands our understanding of the intricate cytokine network but also positions it as a compelling potential therapeutic target. Investigating IL-39's precise mechanisms and contributions to human diseases offers promising avenues for developing novel biologics or small-molecule inhibitors to treat refractory autoimmune disorders.