Genetic and epigenetic regulation of PD-1 expression

APR Bally, JW Austin, JM Boss - The Journal of Immunology, 2016 - journals.aai.org
APR Bally, JW Austin, JM Boss
The Journal of Immunology, 2016journals.aai.org
The inhibitory immune receptor programmed cell death-1 (PD-1) is intricately regulated. In T
cells, PD-1 is expressed in response to most immune challenges, but it is rapidly
downregulated in acute settings, allowing for normal immune responses. On chronically
stimulated Ag-specific T cells, PD-1 expression remains high, leading to an impaired
response to stimuli. Ab blockade of PD-1 interactions during chronic Ag settings partially
restores immune function and is now used clinically to treat a variety of devastating cancers …
Abstract
The inhibitory immune receptor programmed cell death-1 (PD-1) is intricately regulated. In T cells, PD-1 is expressed in response to most immune challenges, but it is rapidly downregulated in acute settings, allowing for normal immune responses. On chronically stimulated Ag-specific T cells, PD-1 expression remains high, leading to an impaired response to stimuli. Ab blockade of PD-1 interactions during chronic Ag settings partially restores immune function and is now used clinically to treat a variety of devastating cancers. Understanding the regulation of PD-1 expression may be useful for developing novel immune-based therapies. In this review, the molecular mechanisms that drive dynamic PD-1 expression during acute and chronic antigenic stimuli are discussed. An array of cis-DNA elements, transcription factors, and epigenetic components, including DNA methylation and histone modifications, control PD-1 expression. The interplay between these regulators fine-tunes PD-1 expression in different inflammatory environments and across numerous cell types to modulate immune responses.
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