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Genetic and epigenetic regulation of PD-1 expression1 #MMPMID26945088
Bally AP; Austin JW; Boss JM
J Immunol 2016[Mar]; 196 (6): 2431-7 PMID26945088show ga
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 is rapidly down regulated in acute settings, allowing for normal immune responses. On chronically stimulated antigen-specific T cells, PD-1 expression remains high, leading to an impaired response to stimuli. Antibody blockade of PD-1 interactions during chronic antigen 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. Here, the molecular mechanisms that drive dynamic PD-1 expression during acute and chronic antigenic stimuli are reviewed. 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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J+Immunol 2016 ; 196 (6): 2431-7
