Pro-inflammatory granzyme K contributes extracellularly to disease

Granzyme K (GzmK) is an immune-secreted serine protease typically expressed at low levels but elevated in response to tissue injury and disease. Known as an orphan granzyme due to limited scientific investigation, this tryptase is being redefined as having important roles in inflammation and disease...

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Main Author: Christopher T. Turner
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1620670/full
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author Christopher T. Turner
author_facet Christopher T. Turner
author_sort Christopher T. Turner
collection DOAJ
description Granzyme K (GzmK) is an immune-secreted serine protease typically expressed at low levels but elevated in response to tissue injury and disease. Known as an orphan granzyme due to limited scientific investigation, this tryptase is being redefined as having important roles in inflammation and disease pathogenesis. Multiple GzmK expressing CD8+ T cell subsets are being identified with augmented expression and important roles in disease. Traditionally recognized as a mediator of cytotoxic lymphocyte-mediated cell death, GzmK’s role is being recharacterized through multiple recently released studies focused on newly identified extracellular mechanisms of action. These studies identify GzmK to be inflammatory, being able to trigger pro-inflammatory cytokine release, enhance immune cell recruitment, exacerbate the immune response to bacterial infections, and activate complement. In multiple disease states, dysregulated GzmK expression and potential accumulation in the extracellular space directly contributes to impaired health outcomes, thereby suggesting downregulation may prevent disease severity. GzmK is therefore emerging as a therapeutic target, potentially valuable in sepsis, pulmonary disease, inflammatory skin disease, rheumatoid arthritis and even aging.
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spelling doaj-art-7aefd0ee208240d5955c2a0dbbf81e832025-08-20T02:07:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16206701620670Pro-inflammatory granzyme K contributes extracellularly to diseaseChristopher T. TurnerGranzyme K (GzmK) is an immune-secreted serine protease typically expressed at low levels but elevated in response to tissue injury and disease. Known as an orphan granzyme due to limited scientific investigation, this tryptase is being redefined as having important roles in inflammation and disease pathogenesis. Multiple GzmK expressing CD8+ T cell subsets are being identified with augmented expression and important roles in disease. Traditionally recognized as a mediator of cytotoxic lymphocyte-mediated cell death, GzmK’s role is being recharacterized through multiple recently released studies focused on newly identified extracellular mechanisms of action. These studies identify GzmK to be inflammatory, being able to trigger pro-inflammatory cytokine release, enhance immune cell recruitment, exacerbate the immune response to bacterial infections, and activate complement. In multiple disease states, dysregulated GzmK expression and potential accumulation in the extracellular space directly contributes to impaired health outcomes, thereby suggesting downregulation may prevent disease severity. GzmK is therefore emerging as a therapeutic target, potentially valuable in sepsis, pulmonary disease, inflammatory skin disease, rheumatoid arthritis and even aging.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1620670/fullgranzymeinflammationserine proteaseCD8 lymphocytes +cytotoxicity and immune system
spellingShingle Christopher T. Turner
Pro-inflammatory granzyme K contributes extracellularly to disease
Frontiers in Immunology
granzyme
inflammation
serine protease
CD8 lymphocytes +
cytotoxicity and immune system
title Pro-inflammatory granzyme K contributes extracellularly to disease
title_full Pro-inflammatory granzyme K contributes extracellularly to disease
title_fullStr Pro-inflammatory granzyme K contributes extracellularly to disease
title_full_unstemmed Pro-inflammatory granzyme K contributes extracellularly to disease
title_short Pro-inflammatory granzyme K contributes extracellularly to disease
title_sort pro inflammatory granzyme k contributes extracellularly to disease
topic granzyme
inflammation
serine protease
CD8 lymphocytes +
cytotoxicity and immune system
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1620670/full
work_keys_str_mv AT christophertturner proinflammatorygranzymekcontributesextracellularlytodisease