Galectin-9: A Multifaceted Immune Regulator with Therapeutic Potential
Structure and Expression
Galectin-9 (GAL9) is one of the members of galectin family of proteins which is characterized by the presence of a tandem repeat of carbohydrate recognition domain (CRD). The protein contains two structurally and functionally similar CRDs that are connected by a variable flexible linker peptide. Thus, the GAL9 can build lattices and cross-link various glycoproteins, that is why this protein performs a wide range of functions. GAL9 is present in almost all the tissues of the body and is also synthesized by different cell types including the immune cells, endothelial cells and epithelial cells. It has been reported that the level of GAL9 is up regulated by various stimuli including interferon-γ, a pro-inflammatory cytokine thus playing a crucial role in inflammation.
Immunological Functions
Gal9 is a critical immunological checkpoint molecule that acts mainly by binding to TIM-3 on T-cells. This interaction is very important in the regulation of T-cells whereby it leads to induction of T-cell apoptosis and suppression of Th1 and Th17 responses. Furthermore, GAL9 is involved in the proliferation as well as the function of T-regulatory cells which are normally involved in the regulation of immune tolerance as well as the prevention of autoimmunity. The protein also regulates other immune cells such as dendritic cells and natural killer cells thus having effects on both the innate and adaptive immune systems.
Role in Disease and Pathology
GAL9 has been found to be associated with numerous pathological conditions. In cancer, GAL9 can have dual role depending on the context as it can enhance anti-tumor immunity in some situations while at the same time it can promote tumor immune evasion due to its immunosuppressive function. In viral infections GAL9 levels are usually up regulated and are in line with the disease of severity chronic especially viral in infections cases including HIV and hepatitis B. The protein is also involved in autoimmune diseases and its expression is usually altered in such conditions. This has made researchers and scientists develop an interest in using GAL9 either as a biomarker for diagnosis or as a target for therapy.
Therapeutic Applications and Clinical Development
There is an ever-increasing focus on the therapeutic effects of GAL9 in the current literature. In the cancer immunotherapy field, strategies that focus on the GAL9-TIM-3 pathway are being explored as potential new ways of treatment either alone or in combination with the current checkpoint blockers. There are ongoing clinical trials that aim at using GAL9 antagonists to boost the antitumor immunity as well as GAL9 agonists to induce tolerance in the immune system in autoimmune diseases. The functions of the protein in viral infections have also created an interest in the development of GAL9 based antiviral approaches.
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