About this Research Topic
Granzymes are a family of serine proteases previously believed to play exclusive and somewhat redundant roles in lymphocyte-mediated target cell death. However, recent studies have challenged this paradigm. Distinct substrate profiles and functions have since emerged for each granzyme while their dysregulated proteolytic activities have been linked to diverse pathologies. Expressed at low levels in healthy tissue, granzymes are upregulated and contribute to diseases as varied as aging, tissue injury, inflammatory diseases, and autoimmunity. Notably, emerging evidence identifies granzymes to be secreted, functioning extracellularly, and interacting with a range of substrates. As this understanding of granzymes evolves, we need to reassess earlier studies through a new, non-cytotoxicity-focused lens. The functions of granzymes are being further delineated with advanced genomics, proteomics, degradomics and other tools, likely resulting in the identification of other pathophysiological roles for granzymes. Based on this new evidence, granzymes have therefore emerged as therapeutic targets with high 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 pathologic disease processes, including (but not limited to) autoimmunity, aging, inflammation, and cancer.
• This includes the roles of granzymes in T-cell and NK cell mediated apoptosis.
• Also encapsulates emerging extracellular granzyme roles in response to inflammation.
• And, includes granzymes effect on immune cell senescence in extrinsic and intrinsic aging processes.
• Can also include breakthroughs in techniques to better characterise or monitor granzyme expression in biological systems.
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 pathologic disease processes, including (but not limited to) autoimmunity, aging, inflammation, and cancer.
• This includes the roles of granzymes in T-cell and NK cell mediated apoptosis.
• Also encapsulates emerging extracellular granzyme roles in response to inflammation.
• And, includes granzymes effect on immune cell senescence in extrinsic and intrinsic aging processes.
• Can also include breakthroughs in techniques to better characterise or monitor granzyme expression in biological systems.
Keywords: Granzyme, inflammation, immune-secreted proteases, aging, autoimmunity, tissue repair
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