Interleukin-35 (IL-35) (IL-35)

Interleukin-35 (IL-35) is a member of the IL-12 family of cytokines, uniquely characterized by its potent immunosuppressive properties. It is a heterodimer composed of the Epstein-Barr virus-induced gene 3 (EBI3) and the p35 subunit of IL-12 (Collison et al., Nature, 2007). Primarily secreted by regulatory T cells (Tregs) and regulatory B cells (Bregs), IL-35 acts on effector T cells to inhibit their proliferation and cytokine production, often through a receptor complex consisting of IL-12Rβ2 and gp130 (Sawant et al., Nat Immunol, 2015). In the context of oncology, IL-35 is frequently exploited by tumors to create an immunosuppressive microenvironment, leading to T cell exhaustion and resistance to immunotherapy (Turnis et al., J Clin Invest, 2016). Because of its role in dampening immune responses, IL-35 is a significant target for drug development; neutralizing antibodies are being explored to treat various cancers, while IL-35-based therapies are being investigated for their potential to treat autoimmune and inflammatory diseases like rheumatoid arthritis and multiple sclerosis.

Other names

IL35Interleukin 35EBI3/p35 heterodimerEpstein-Barr virus-induced gene 3/Interleukin-12 subunit alpha complex

Neutralization of IL-35 prevents the suppression of effector T cells (CD4+ and CD8+) and inhibits the conversion of conventional T cells into suppressive iTr35 cells, thereby enhancing anti-tumor immunity (Turnis et al., J Clin Invest, 2016). Alternatively, IL-35 supplementation or agonism suppresses pathogenic T cell responses in autoimmune contexts (Collison et al., Nature, 2007).