title: CD200 is a novel p53-target gene involved in apoptosis-associated immune tolerance.
abstract: During apoptotic cell death, biochemical processes modify self-proteins and create potential autoantigens. To maintain self-tolerance in the face of natural cell turnover, the immune system must prevent or control responses to apoptosis-associated autoantigens or risk autoimmunity. The molecular mechanisms governing this process remain largely unknown. Here, we show that expression of the immunoregulatory protein CD200 increases as murine dendritic cells (DCs) undergo apoptosis. We define CD200 as a p53-target gene and identify both p53- and caspase-dependent pathways that control CD200 expression during apoptosis. CD200 expression on apoptotic DCs diminishes proinflammatory cytokine production in response to self-antigens in vitro and is required for UVB-mediated tolerance to haptenated self-proteins in vivo. Up-regulation of CD200 may represent a novel mechanism, whereby immune reactivity to apoptosis-associated self-antigens is suppressed under steady state conditions.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Rosenblum
authors.forename: Edit
authors.initials: E
authors.lastname: Olasz
authors.forename: Jeffery E
authors.initials: JE
authors.lastname: Woodliff
authors.forename: Bryon D
authors.initials: BD
authors.lastname: Johnson
authors.forename: Marja C
authors.initials: MC
authors.lastname: Konkol
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Gerber
authors.forename: Rimas J
authors.initials: RJ
authors.lastname: Orentas
authors.forename: Gordon
authors.initials: G
authors.lastname: Sandford
authors.forename: Robert L
authors.initials: RL
authors.lastname: Truitt
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000235:genetics*; D017209:Apoptosis / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D016158:Genes, p53 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007438:Introns / Q000235:genetics; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D017931:DNA Primers; D012333:RNA, Messenger; C042739:antigens, CD200