Epstein-Barr virus-induced gene 3 (EBI3)

Epstein-Barr virus-induced gene 3 (EBI3) is a secreted glycoprotein and a member of the interleukin-12 (IL-12) cytokine family [UniProt Q14213]. It serves as a critical beta-subunit that heterodimerizes with various alpha-subunits to form distinct cytokines: with p35 to form IL-35, with p28 to form IL-27, and with p19 to form IL-39 [NIH, 2026]. IL-35 is primarily produced by regulatory T cells (Tregs) and regulatory B cells (Bregs), where it exerts potent immunosuppressive and anti-inflammatory effects by inhibiting effector T-cell proliferation and promoting the expansion of induced regulatory T cells (iTr35) [Frontiers in Immunology, 2026]. In the context of oncology, EBI3 and IL-35 are often upregulated in the tumor microenvironment, contributing to immune evasion, angiogenesis, and poor prognosis across various cancers, including lung and pancreatic adenocarcinoma [AACR, 2021; PubMed, 21849417]. Conversely, in autoimmune and inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus, EBI3-containing cytokines play a protective role by dampening excessive immune responses [NIH, 2026]. Therapeutic strategies currently under investigation include neutralizing antibodies to block EBI3/IL-35 in cancer and recombinant proteins or mRNA-based therapies to augment its signaling in autoimmune conditions [OSE Immunotherapeutics, 2024; NIH, 2017].

Other names

IL-27 subunit betaIL-27BIL-35 subunit betaIL35BEpstein-Barr virus-induced gene 3 proteinEBV-induced gene 3 protein

Modulation of IL-35 signaling; antagonism for cancer therapy to restore anti-tumor immunity, or agonism for autoimmune diseases to suppress inflammation [Frontiers in Immunology, 2026; AACR, 2021].