Interleukin-35 (IL-35)

Interleukin-35 (IL-35) is a dimeric, immunosuppressive cytokine belonging to the interleukin-12 (IL-12) family, formed by the IL-12α (p35) and IL-27β (EBI3) subunits[1][3][5]. Unlike other cytokines in its family, IL-35 is primarily secreted by regulatory T cells (Tregs), regulatory B cells (Bregs), CD8+ Tregs, and certain dendritic cells, predominantly in response to inflammatory cues[1][3][5]. IL-35 signals through several receptor combinations, mainly involving IL-12Rβ2 and gp130 or IL-27Rα chains, activating STAT1 and STAT3 in target cells[1][2][3][5]. Its core biological role is to suppress effector T cell activity (notably Th1 and Th17) and amplify regulatory cell populations, thereby attenuating inflammation and autoimmunity[1][2][3][5][7]. IL-35 has been implicated in a range of diseases, including autoimmune conditions, cancers (often acting as a tumor-promoting immunosuppressive factor), and infectious or inflammatory diseases, where it can serve both protective and pathogenic roles depending on context[2][3][4][6][7][8]. No approved targeted drugs exist for IL-35, but it is under active investigation as both a therapeutic and biomarker target in immune-mediated diseases[5][6][7].

Other names

IL-35IL35EBI3-p35 heterodimer

Immunosuppression via STAT1/STAT3 pathway activation in Tregs and Bregs. Promotion of induced regulatory T cells (iTr35). Inhibition of proinflammatory cytokine production.