Recombinant Human TNFSF18 protein

TNFSF18 (Tumor Necrosis Factor Superfamily Member 18), also known as GITR Ligand (GITRL) or AITRL, is a type II transmembrane protein belonging to the TNF superfamily. It plays a critical role in immune regulation by interacting with its receptor, GITR (Glucocorticoid-Induced TNFR-Related Protein), which is expressed on activated T cells, regulatory T cells (Tregs), and innate immune cells. The TNFSF18-GITR axis modulates T-cell activation, differentiation, and survival, balancing immune responses between tolerance and inflammation. TNFSF18 exists in both membrane-bound and soluble forms, with the latter generated through proteolytic cleavage or alternative splicing.

Recombinant TNFSF18 protein is typically produced using mammalian expression systems (e.g., HEK293 or CHO cells) or bacterial systems to ensure proper folding and bioactivity. It retains the functional TNF homology domain, enabling receptor binding and downstream signaling. Studies highlight its dual role: enhancing effector T-cell responses while suppressing Treg-mediated immune suppression, making it a potential therapeutic target in cancer immunotherapy. Conversely, its dysregulation is linked to autoimmune diseases, suggesting context-dependent effects.

In research, recombinant TNFSF18 is used to study immune checkpoint pathways, evaluate GITR-targeting therapies, or develop combination strategies with PD-1/CTLA-4 inhibitors. Preclinical models demonstrate that GITR agonism can promote antitumor immunity by boosting CD8+ T-cell function and destabilizing Tregs. However, clinical trials have shown mixed outcomes, underscoring the need for optimized dosing and biomarker selection. Beyond oncology, TNFSF18 recombinant protein aids in exploring autoimmune mechanisms and tolerance induction. Its versatility in modulating adaptive immunity continues to drive interest in both therapeutic and mechanistic investigations.