Pro-inflammatory granzyme K contributes extracellularly to disease

Area of Science:

• Immunology
• Molecular Biology
• Pathogenesis

Background:

• Granzyme K (GzmK) is an immune-secreted serine protease with low basal expression, but elevated levels are observed during tissue injury and disease.
• Historically considered an 'orphan granzyme' due to limited research, GzmK is now recognized for significant roles in inflammation and disease development.
• Recent studies highlight GzmK's involvement in various CD8+ T cell subsets, with augmented expression linked to disease pathology.

Purpose of the Study:

• To recharacterize the role of Granzyme K (GzmK) beyond its traditional function in cell death.
• To explore the newly identified extracellular mechanisms of GzmK action.
• To investigate the therapeutic potential of targeting GzmK in various inflammatory and age-related diseases.

Main Methods:

• Review of recently released studies focusing on Granzyme K's extracellular functions.
• Analysis of GzmK's pro-inflammatory activities, including cytokine release and immune cell recruitment.
• Examination of GzmK's role in bacterial infections and complement activation.

Main Results:

• GzmK exhibits inflammatory properties, triggering pro-inflammatory cytokine release and enhancing immune cell recruitment.
• Extracellular GzmK exacerbates immune responses to bacterial infections and activates the complement system.
• Dysregulated GzmK expression and accumulation contribute to impaired health outcomes in various diseases.

Conclusions:

• Granzyme K's function is being redefined, revealing significant pro-inflammatory and pathogenic roles.
• Extracellular GzmK contributes to disease severity, suggesting downregulation as a potential therapeutic strategy.
• GzmK is an emerging therapeutic target for conditions including sepsis, pulmonary disease, inflammatory skin conditions, rheumatoid arthritis, and aging.