Epstein-Barr virus-induced gene 3 (EBI3) (EBI3)

Epstein-Barr virus-induced gene 3 (EBI3) is a secreted glycoprotein that serves as a critical subunit for several heterodimeric cytokines within the interleukin-12 (IL-12) family, most notably Interleukin-27 (IL-27) and Interleukin-35 (IL-35) (UniProt P78545). Structurally related to the p40 subunit of IL-12 and the soluble IL-6 receptor, EBI3 plays a dualistic role in the immune system by modulating both pro-inflammatory and anti-inflammatory pathways (PubMed 31435275). In the context of IL-27, it influences T-cell differentiation and can limit excessive inflammation, whereas in IL-35, it acts as a potent immunosuppressive factor primarily produced by regulatory T cells (PubMed 28213285). Pathologically, EBI3 is frequently upregulated in various malignancies, including lymphomas and solid tumors, where it facilitates immune evasion by suppressing effector T-cell activity and promoting an exhausted phenotype (PubMed 31435275). Consequently, EBI3 and its associated cytokine complexes have emerged as promising therapeutic targets in oncology and autoimmune disorders. Current drug development efforts, such as the monoclonal antibody SRF388, focus on neutralizing these cytokines to restore anti-tumor immunity or dampen pathological inflammation (ClinicalTrials.gov NCT04374877).

Other names

Interleukin-27 subunit betaIL-27BIL27BEBV-induced gene 3 protein

Neutralization of IL-27 or IL-35 signaling to enhance anti-tumor immunity or modulate inflammatory responses.