Abstract
Natural killer (NK) cells are cytotoxic innate lymphocytes that play an important role in immune surveillance. The development, maturation and effector functions of NK cells are orchestrated by the T-box transcription factor T-bet, whose expression is induced by cytokines such as IFN-γ, IL-12, IL-15 and IL-21 through the respective cytokine receptors and downstream JAK/STATs or PI3K-AKT-mTORC1 signaling pathways. In this review, we aim to discuss the expression and regulation of T-bet in NK cells, the role of T-bet in mouse NK cell development, maturation, and function, as well as the role of T-bet in acute, chronic infection, inflammation, autoimmune diseases and tumors.
Highlights
The transcription factor T-bet is an important transcription factor for the immune system, orchestrating multiple types and aspects of immune responses
After 24 hours of stimulation, the level of IFN-g produced by T-bet-/-Natural killer (NK) cells was significantly lower than that of WT mice. These findings indicate that the early and rapid secretion of IFN-g is independent of T-bet, but T-bet expression is required for the maintenance of IFN-g production by NK cells [14]
T-bet was down-regulated in adoptively transferred NK cells upon exposure to tumors and proliferation, which was associated with downregulation of activating receptors and IFN-g [86]
Summary
The transcription factor T-bet ( known as Tbx21) is an important transcription factor for the immune system, orchestrating multiple types and aspects of immune responses. Based on the knowledge of the expression regulation and function of T-bet in NK cells, we discuss potential immunotherapy strategies that could exploit the anti-tumor capacity of NK cells in future.
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