Granzymes, a family of serine proteases, were once thought to have overlapping roles primarily in lymphocyte-driven cell death. However, recent research has shifted this view, revealing unique substrate profiles and functions for each granzyme. Their dysregulated activity is now linked to various diseases, such as aging, tissue injury, inflammatory conditions, and autoimmunity. Although granzymes are typically expressed at low levels in healthy tissues, they are upregulated during disease states.
Notably, new evidence shows that granzymes can be secreted and function extracellularly, interacting with a wide array of substrates. This evolving understanding urges us to revisit past research with a perspective that extends beyond cytotoxicity. Advanced genomics, proteomics, and degradomics tools are further clarifying the roles of granzymes, which may lead to the discovery of additional pathophysiological functions. Consequently, granzymes have emerged as promising therapeutic targets with significant clinical potential.
The previous dogma thought granzymes to only function intracellularly, acting to induce apoptosis of cancer and virus infected cells. New roles for granzymes are being uncovered all the time and in various disease modalities, including aging, autoimmunity, and tissue repair. The purpose of the present review is to provide insights into the non-cytotoxic functions of granzymes and contextualize the relevant literature within the framework of health and disease.
We welcome manuscripts focusing on, but not limited to, the following sub-topics:
- Roles of granzymes and other immune-secreted proteases in pathological disease processes
- The involvement of granzymes in T-cell and NK cell-mediated apoptosis
- Emerging extracellular functions of granzymes in inflammatory responses
- Impact of granzymes on immune cell senescence in both extrinsic and intrinsic aging processes
- Advances in techniques for characterizing or monitoring granzyme expression in biological systems
Granzymes, a family of serine proteases, were once thought to have overlapping roles primarily in lymphocyte-driven cell death. However, recent research has shifted this view, revealing unique substrate profiles and functions for each granzyme. Their dysregulated activity is now linked to various diseases, such as aging, tissue injury, inflammatory conditions, and autoimmunity. Although granzymes are typically expressed at low levels in healthy tissues, they are upregulated during disease states.
Notably, new evidence shows that granzymes can be secreted and function extracellularly, interacting with a wide array of substrates. This evolving understanding urges us to revisit past research with a perspective that extends beyond cytotoxicity. Advanced genomics, proteomics, and degradomics tools are further clarifying the roles of granzymes, which may lead to the discovery of additional pathophysiological functions. Consequently, granzymes have emerged as promising therapeutic targets with significant clinical potential.
The previous dogma thought granzymes to only function intracellularly, acting to induce apoptosis of cancer and virus infected cells. New roles for granzymes are being uncovered all the time and in various disease modalities, including aging, autoimmunity, and tissue repair. The purpose of the present review is to provide insights into the non-cytotoxic functions of granzymes and contextualize the relevant literature within the framework of health and disease.
We welcome manuscripts focusing on, but not limited to, the following sub-topics:
- Roles of granzymes and other immune-secreted proteases in pathological disease processes
- The involvement of granzymes in T-cell and NK cell-mediated apoptosis
- Emerging extracellular functions of granzymes in inflammatory responses
- Impact of granzymes on immune cell senescence in both extrinsic and intrinsic aging processes
- Advances in techniques for characterizing or monitoring granzyme expression in biological systems