Transcriptional and epigenetic regulation of PD-1 expression

Programmed cell death-1 (PD-1) is a co-inhibitory receptor that plays important roles in regulating T cell immunity and peripheral tolerance. PD-1 signaling prevents T cells from overactivation during acute infections, but it maintains T cell exhaustion during chronic infections. Tumor cells can exploit the PD-1 signaling pathway to evade antitumor immune responses. The PD-1 signaling pathway is also essential for maintaining peripheral tolerance and prevention of autoimmunity. PD-1 expression is strictly and differentially regulated by diverse mechanisms in immune cells. It is activated and repressed by distinct transcription factors in different circumstances. Moreover, epigenetic mechanisms are also involved in regulating PD-1 expression. In this review, we summarize the knowledge of the transcriptional and epigenetic regulation of PD-1 expression during different immune responses.