Deciphering Natural Killer Cell Homeostasis

Abstract

Natural killer (NK) cells have a central role within the innate immune system, eliminating virally infected, foreign and transformed cells through their natural cytotoxic capacity. Release of their cytotoxic granules is tightly controlled through the balance of a large repertoire of inhibitory and activating receptors, and it is the unique combination of these receptors expressed by individual cells that confers immense diversity both in phenotype and functionality. The diverse, yet unique, NK cell repertoire within an individual is surprisingly stable over time considering the constant renewal of these cells at steady state. Here we give an overview of NK cell differentiation and discuss metabolic requirements, intra-lineage plasticity and transcriptional reprogramming during IL-15-driven homeostatic proliferation. New insights into the regulation of NK cell differentiation and homeostasis could pave the way for the successful implementation of NK cell-based immunotherapy against cancer.

FAM13A regulates KLRG1 expression and interferon gamma production of natural killer cells

“…Finally, the confinement model was also proposed, taking into account the adhesion molecules (He and Tian 2017). More recently, from a mechanistic point of view, the presence of dense-core secretory lysosomes containing the cytolytic effector protein granzyme B distinguishes educated from uneducated resting NK cells (Goodridge et al 2019, Pfefferle et al 2020). Kim et al have revealed that the IR from the Ly49 family can efficiently license NK cells (Kim et al 2005).…”

Generating natural killer cells for adoptive transfer: expanding horizons

“…Interestingly, cells that acquired phenotypes of the greatest proliferative potential were least cytotoxic and most prone to apoptosis. Understanding the impact of such finely balanced homeostatic mechanisms in the artificial environment of ex vivo NK cell expansion may ultimately redefine an "ideal" donor and expanded cell composition [41]. "Adaptive" or "memory-like" NK cells are a subset of therapeutic interest because of their improved survival and cytolytic capabilities [42].…”

Immunocyte Membrane-Coated Nanoparticles for Cancer Immunotherapy

“…NK cells are unique lymphocytes that can recognize and kill aberrant cells without antibodies or major histocompatibility complex (MHC) [ 48 ]. Therefore, NK cells are key for tumor cell surveillance, because tumor cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T-cells [ 49 ]. Although NK cells lack antigen-specific cell surface receptors, they have many alternative receptors that can recognize tumor cells, including NKG2D, NKp44, NKp46, NKp30, and DNAM [ 50 , 51 ].…”