Nkg7-flox Mouse

Nkg7, or natural killer cell granule protein-7, is a cytolytic granule-associated molecule expressed in cytotoxic lymphocytes such as CD8+ T cells and natural killer (NK) cells. It plays a crucial role in the cytotoxic function of these cells, regulating processes like cytolytic granule exocytosis, trafficking, and calcium release, and is involved in controlling inflammation [1,3,4,5]. It may also regulate endosomal vesicle trafficking, though the precise mechanism is not fully resolved [4].

In Nkg7-deficient mice, neoantigen-expressing mouse tumors grew faster, and the efficacy of single or combination immune checkpoint blockade (ICB) was significantly reduced, indicating Nkg7 is required for optimal antitumor T-cell immunity and for the accumulation of T cells in the tumor microenvironment [2]. Deletion of NKG7 in CD8+ T cells reduces their ability to degranulate and kill target cells in vitro, but due to inefficient cytotoxic activity, they form a prolonged immune synapse with tumor cells, leading to increased secretion of inflammatory cytokines [3]. In a type 1 diabetes mellitus (T1DM) rat model, silencing Nkg7 prevented T lymphocyte activation and proliferation, reducing the number of T lymphocytes in the pancreatic islet and alleviating pancreatic islet β-cell damage [6].

In conclusion, Nkg7 is essential for the cytotoxic function of CD8+ T cells and NK cells, playing a key role in antitumor immunity and T-cell-mediated immune responses. Studies using Nkg7-deficient mouse models have revealed its importance in tumor control, ICB efficacy, and in the context of T1DM, providing valuable insights into its function in disease-related immune processes.