Recombinant Human IL35 protein

Interleukin-35 (IL-35), a member of the interleukin-12 (IL-12) cytokine family, is an immunosuppressive heterodimeric protein composed of Epstein-Barr virus-induced gene 3 (EBI3) and interleukin-12 alpha (IL-12α/p35) subunits. First identified in 2007 as a product of regulatory T cells (Tregs), IL-35 distinguishes itself from other IL-12 family cytokines by its unique role in immune suppression. It is primarily secreted by Tregs and certain B cells (Bregs) to mediate tolerance and limit excessive inflammatory responses. Structurally, IL-35 requires the pairing of EBI3 and p35 subunits, which form a functional heterodimer through disulfide bonds. Unlike IL-12 or IL-23. IL-35 signals through a distinct receptor complex involving IL-12Rβ2 and gp130 subunits, activating STAT1/STAT4 pathways in T cells to promote immunosuppression.

Biologically, IL-35 suppresses effector T cell proliferation, induces the conversion of conventional T cells into regulatory phenotypes (iTreg35), and inhibits pro-inflammatory cytokine production. Its immunosuppressive functions are implicated in autoimmune diseases, cancer, and chronic infections. For instance, elevated IL-35 levels correlate with tumor progression by fostering an immune-tolerant microenvironment, while its deficiency exacerbates autoimmune conditions like colitis or rheumatoid arthritis.

Recombinant IL-35 protein is produced using mammalian expression systems (e.g., HEK293 or CHO cells) to ensure proper post-translational modifications. Purification typically involves affinity chromatography tags (e.g., His-tag) fused to one subunit. Research applications include studying immune tolerance mechanisms, developing therapeutic strategies for autoimmune disorders, and exploring its dual roles in cancer immunotherapy. However, challenges remain in understanding context-dependent functions and optimizing clinical applications due to its pleiotropic effects.