The study reveals that granzyme K (GZMK), traditionally known for inducing cell death through proteolysis, plays a crucial role in inflammation by activating the complement cascade. This cascade is essential for immune responses in diseases such as rheumatoid arthritis (RA). GZMK acts specifically on C2 and C4, crucial proteins within this cascade, ultimately leading to the generation of inflammatory mediators. Notably, the research highlights that GZMK is particularly enriched in inflamed tissues, linking it directly to complement activation and suggesting its importance in the pathogenesis of RA and possibly other inflammatory diseases.
We demonstrate that granzyme K (GZMK), previously associated with cell death, plays a crucial role in triggering the inflammatory response by activating the complement cascade.
Our findings indicate that granzyme K cleaves C2 and C4, forming C3 convertase, which is pivotal in generating multiple effector molecules essential for the complement immune response.
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