title: Genetic and Epigenetic Regulation of PD-1 Expression.
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.
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Alexander P R
authors.identifier: http://orcid.org/0000-0003-4494-5033
authors.initials: AP
authors.lastname: Bally
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: James W
authors.initials: JW
authors.lastname: Austin
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 jmboss@emory.edu.
authors.forename: Jeremy M
authors.identifier: http://orcid.org/0000-0002-2432-1840
authors.initials: JM
authors.lastname: Boss
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology
chemical_list: D061026:Programmed Cell Death 1 Receptor