Untersuchung der pathophysiologischen Rolle von Granzym K bei viralen Infektionen und Sepsis
Zusammenfassung der Projektergebnisse
The biological role of granzyme K, a serine protease of cytotoxic T lymphocytes (CTL), is controversial. It has been reported to induce perforin-mediated cell death in vitro, but is also reported to be non-cytotoxic and to operate in inflammatory processes. To elucidate the biological role of this protease we have deleted the granzyme K gene in mice (mutant allele: Gzmktm1.1Pib; MGI:5636646). Gzmk-/- mice are healthy, anatomically normal, fecund, and show normal hematopoietic development. Gzmk-/- mice readily recover from Lymphocytic choriomeningitis virus and mouse pox Ectromelia virus infection. Ex vivo, virus-specific granzyme K – deficient CTL are indistinguishable from those of wild type mice in apoptosis induction of target cells. These data suggest that granzyme K does not play an essential role in viral immunity or cytotoxicity. Our granzyme K knockout line completes the collection of mouse models for the human granzymes, and will further our understanding of their biological roles and relationships.
Projektbezogene Publikationen (Auswahl)
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Are all granzymes cytotoxic in vivo? Biol Chem 2013
Joeckel, Lars T. & Bird, Phillip I.
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Blessing or curse? Proteomics in granzyme research. Proteomics Clin Appl 2014
Joeckel, Lars T. & Bird, Phillip I.
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Serpinb9 is a marker of antigen cross-presenting dendritic cells. Mol Immunol 2017
Mangan, M.S.; Vega-Ramos, J.; Joeckel, L.T.; Mitchell, A.J.; Rizzitelli, A.; Roediger, B.; Kaiserman, D.; Weninger, W.W.; Villadangos, J.A. & Bird, P.I.
