CD200 is a novel p53-target gene involved in apoptosis-associated immune tolerance.
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.
Rosenblum
Michael D
MD
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226, USA.
Olasz
Edit
E
Woodliff
Jeffery E
JE
Johnson
Bryon D
BD
Konkol
Marja C
MC
Gerber
Kimberly A
KA
Orentas
Rimas J
RJ
Sandford
Gordon
G
Truitt
Robert L
RL
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
D015703:Antigens, CD; D000954:Antigens, Surface; D017931:DNA Primers; D012333:RNA, Messenger; C042739:antigens, CD200