CD200 is a novel p53-target gene involved in apoptosis-associated immune tolerance. Blood 2004 Apr 01;103(7):2691-8
Date
12/03/2003Pubmed ID
14644999DOI
10.1182/blood-2003-09-3184Scopus ID
2-s2.0-1642414806 (requires institutional sign-in at Scopus site) 73 CitationsAbstract
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.
Author List
Rosenblum MD, Olasz E, Woodliff JE, Johnson BD, Konkol MC, Gerber KA, Orentas RJ, Sandford G, Truitt RLAuthors
Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of WisconsinEdit Olasz PhD, MD Associate Professor in the Dermatology department at Medical College of Wisconsin
Robert L. Truitt PhD Emeritus Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntigens, CD
Antigens, Surface
Apoptosis
Base Sequence
Cells, Cultured
DNA Primers
Dendritic Cells
Genes, p53
Humans
Immune Tolerance
Introns
Lymphocyte Culture Test, Mixed
Lymphocytes
Mice
Mice, Inbred C57BL
Mice, Knockout
RNA, Messenger
Transcription, Genetic
Tumor Cells, Cultured
Ultraviolet Rays
