ReviewFrontiers in immunology2020
The Multifaceted Function of Granzymes in Sepsis: Some Facts and a Lot to Discover.
Review in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Intracellular expression of granzymes A, B, K and M in blood lymphocyte subsets of critically ill patients with or without sepsis.Clinical and experimental immunology · 2021Trial
- Circulating granzyme A is elevated within the dysregulated host response and associates with mortality in abdominal sepsis.Frontiers in immunology · 2026Article
- Bioinformatics analysis of pyroptosis-related differentially expressed genes in sepsis and diabetes mellitus.PloS one · 2026Article
- Dynamic changes of natural killer cell immunophenotypes and receptors according to the mortality in the intra-abdominal murine sepsis model.Intensive care medicine experimental · 2025Article
- Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis.International journal of molecular sciences · 2025Review
- Upregulation ofInternational journal of molecular sciences · 2025Article
- Association Between Plasma Granzyme B Levels, Organ Failure, and 28-Day Mortality Prediction in Patients with Sepsis.Journal of clinical medicine · 2025Article
- Decoding monocyte heterogeneity in sepsis: a single-cell apoptotic signature for immune stratification and guiding precision therapy.Frontiers in pharmacology · 2025Article
- Changes in immune cell signatures during early infection reflect decoupling of capillary perfusion and glycocalyx dimensions.Frontiers in immunology · 2025Observational
- In-depth analysis of the interplay between oncogenic mutations and NK cell-mediated cancer surveillance in solid tumors.Oncoimmunology · 2024Review
- Granzymes in health and diseases: the good, the bad and the ugly.Frontiers in immunology · 2024Review
- Article
- The shared circulating diagnostic biomarkers and molecular mechanisms of systemic lupus erythematosus and inflammatory bowel disease.Frontiers in immunology · 2024Article
- Distinct immune microenvironment of lung adenocarcinoma in never-smokers from smokers.Cell reports. Medicine · 2023Article
- Rapid, High-Throughput Single-Cell Multiplex In Situ Tagging (MIST) Analysis of Immunological Disease with Machine Learning.Analytical chemistry · 2023Article
- Conformational transition of the Ixodes ricinus salivary serpin Iripin-4.Acta crystallographica. Section D, Structural biology · 2023Article
- Identification of Genes Associated with Decreasing Abundance of Monocytes in Long-Term Peritoneal Dialysis Patients.International journal of general medicine · 2023Article
- Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women-a single-cell RNA transcriptome study during the implantation window.Frontiers in endocrinology · 2023Article
- CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in uterine corpus endometrial carcinoma.Frontiers in oncology · 2023Article
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis is a serious global health problem. In addition to a high incidence, this syndrome has a high mortality and is responsible for huge health expenditure. The pathophysiology of sepsis is very complex and it is not well-understood yet. However, it is widely accepted that the initial phase of sepsis is characterized by a hyperinflammatory response while the late phase is characterized by immunosuppression and immune anergy, increasing the risk of secondary infections. Granzymes (Gzms) are a family of serine proteases classified according to their cleavage specificity. Traditionally, it was assumed that all Gzms acted as cytotoxic proteases. However, recent evidence suggests that GzmB is the one with the greatest cytotoxic capacity, while the cytotoxicity of others such as GzmA and GzmK is not clear. Recent studies have found that GzmA, GzmB, GzmK, and GzmM act as pro-inflammatory mediators. Specially, solid evidences show that GzmA and GzmK function as extracellular proteases that regulate the inflammatory response irrespectively of its ability to induce cell death. Indeed, studies in animal models indicate that GzmA is involved in the cytokine release syndrome characteristic of sepsis. Moreover, the GZM family also could regulate other biological processes involved in sepsis pathophysiology like the coagulation cascade, platelet function, endothelial barrier permeability, and, in addition, could be involved in the immunosuppressive stage of sepsis. In this review, we provide a comprehensive overview on the contribution of these novel functions of Gzms to sepsis and the new therapeutic opportunities emerging from targeting these proteases for the treatment of this serious health problem.
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