Gzmk, also known as Granzyme K, is a tryptase expressed by certain subsets of T cells. It is involved in immune-related processes, with its expression in CD8+ T cells being of particular significance. Gzmk-expressing CD8+ T cells can influence immune functions and inflammation, potentially through its cleavage of complement components, thus contributing to the activation of the complement cascade [2].

In a mouse asthma model, genetic ablation or pharmacological inhibition of Gzmk after disease onset markedly alleviated tissue pathology and restored lung function, suggesting that Gzmk-expressing CD8+ T cells exacerbate the disease in a proteolytic-activity-dependent manner [2]. In the context of aging, a subpopulation of age-associated GZMK-expressing CD8+ T (Taa) cells was identified in mice. These cells were highly clonal, had specific epigenetic and transcriptional signatures, and developed in response to an aged host environment. In humans, the proportion of circulating GZMK+CD8+ T cells increased during healthy aging [1].

In conclusion, Gzmk, through its expression in CD8+ T cells, plays important roles in inflammatory diseases such as asthma and in the aging-related immune system changes. Mouse models with genetic ablation or inhibition of Gzmk have been crucial in revealing its role in exacerbating airway inflammation, providing potential therapeutic targets for inflammatory airway diseases [1,2].