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The mysterious connection between Granzyme B and immune cells: How does it initiate cell death?
Granzyme B (GrB) is an important therapeutic factor in the complex workings of the immune system, especially secreted by natural killer cells (NK cells) and cytotoxic T cells. Recent studies have shown that GrB is not only a lethal molecule but also involved in a series of important physiological processes, including inflammatory responses and extracellular matrix remodeling.
Granzyme B produces a powerful cell death signal in the body at very low concentrations, making it a mysterious but critical player in the apoptotic process.
Structural characteristics of Granzyme B
Granzyme B is encoded by the GZMB gene in humans and is located on chromosome 14q.11.2. It is 3.2kb in length and contains 5 exons. This enzyme is the most abundant among common human granzymes and acts more efficiently at low concentrations. The structure of GrB consists of two six-stranded β-helices and three transmembrane regions, and it carries out protein cleavage with its specialized active site.
Granzyme B release and mechanism of action
GrB enters target cells by being released together with perforin, which forms pores in the target cell's plasma membrane. Granzyme B can enter cells through these pores, bind to negatively charged receptors on the surface of target cells, undergo endocytosis, and subsequently trigger cell death.
Once inside the target cell, GrB activates multiple apoptotic pathways, including cleavage and activation of caspases, a key step in initiating programmed death.
Granzyme B-mediated apoptosis mechanism
In addition to activating caspases, Granzyme B can also cause mitochondria to release cytochrome c, further promoting the process of cell death. At the same time, GrB also cleaves a variety of proteins related to DNA repair and viral replication in the nucleus, leading to the loss of cellular functions.
Targets of Granzyme B and its effects
The effects of GrB are not limited to cell death, but can also trigger a series of physiological changes, such as degradation of the extracellular matrix, which may lead to tissue inflammation or damage. Concentrations of Granzyme B are often elevated in various disease states, including autoimmune diseases, diabetes, and even cancer.
In autoimmune diseases, Granzyme B generates autoantigens by dissecting antigens and exposing new epitopes, leading to pathological conditions.
The role of Granzyme B in immune regulation
Interestingly, Granzyme B not only plays a role in cytotoxic T cells, but also plays an opposite role in regulatory T cells, helping to regulate autoimmune responses and maintain immune homeostasis.
Granzyme B and disease association
Elevated levels of Granzyme B have been associated with a variety of diseases such as type 1 diabetes, lung disease, and liver disease. More studies have shown that GrB can promote organ rejection and have a negative impact on arthritis and chronic obstructive pulmonary disease.
Future research directions
Although we already know many of Granzyme B's functions, its specific role in various diseases needs to be further explored. Therapeutic measures targeting Granzyme B may provide new opportunities to combat autoimmune diseases in the future.
How many unknown mysteries are waiting to be revealed in the interaction between Granzyme B and the immune system?
