Gzmk-KO Mouse

Gzmk, also known as Granzyme K, is a tryptase that plays a role in the immune system. It is expressed in certain subsets of CD8+ T cells and is involved in enhancing the inflammatory functions of non-immune cells. Granzyme K can cleave many complement components, contributing to the activation of the complement cascade [2].

In mouse models, a subpopulation of age-associated granzyme K (GZMK)-expressing CD8+ T (Taa) cells distinct from T effector memory (Tem) cells was identified. These Taa cells developed in response to an aged host environment, were highly clonal, and had specific epigenetic and transcriptional signatures. Activated Taa cells were the primary source of GZMK [1]. In a mouse asthma model, GZMK-expressing CD8+ T cells exacerbated the disease in a manner dependent on the proteolytic activity of GZMK and complements. Genetic ablation or pharmacological inhibition of GZMK after the disease onset markedly alleviated tissue pathology and restored lung function [2].

In conclusion, Gzmk is crucial in immune-related inflammatory processes. Mouse models, especially those with genetic ablation or inhibition of Gzmk, have revealed its role in age-associated immune dysfunctions and recurrent airway inflammatory diseases. These findings suggest Gzmk as a potential therapeutic target for such conditions [1,2].

References:

1. Mogilenko, Denis A, Shpynov, Oleg, Andhey, Prabhakar Sairam, Colonna, Marco, Artyomov, Maxim N. 2020. Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK+ CD8+ T Cells as Conserved Hallmark of Inflammaging. In Immunity, 54, 99-115.e12. doi:10.1016/j.immuni.2020.11.005. https://pubmed.ncbi.nlm.nih.gov/33271118/

2. Lan, Feng, Li, Jizhou, Miao, Wenxuan, Zhang, Luo, Qi, Hai. 2025. GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases. In Nature, 638, 490-498. doi:10.1038/s41586-024-08395-9. https://pubmed.ncbi.nlm.nih.gov/39814882/