Maturation of Dendritic Cells Is Accompanied by Rapid Transcriptional Silencing of Class II Transactivator (Ciita) Expression

Autor: Luca Bernasconi, Tobias Suter, Jean-Marc Waldburger, Adriano Fontana, Krzysztof Masternak, Walter Reith, Annick Mühlethaler-Mottet, Salomé Landmann, Jean-François Arrighi, Conrad Hauser
Přispěvatelé: University of Zurich, Reith, Walter
Rok vydání: 2001
Předmět:
Transcription
Genetic
RNA
Messenger/genetics/metabolism
Immunology
Alpha interferon
chemical and pharmacologic phenomena
ddc:616.07
bare lymphocyte syndrome
Myelin oligodendrocyte glycoprotein
experimental autoimmune encephalitis
Interferon-gamma
Mice
Antigen
medicine
CIITA
histone deacetylation
Animals
Humans
Immunology and Allergy
Gene silencing
Interferon gamma
RNA
Messenger
Gene Silencing
Promoter Regions
Genetic
Cells
Cultured
DNA Primers
2403 Immunology
Dendritic Cells/ cytology/drug effects
CD40
Base Sequence
biology
class II transactivator
Nuclear Proteins
DNA
Dendritic Cells
Dna
Interferon-gamma/pharmacology
Cell biology
Mice
Inbred C57BL
2723 Immunology and Allergy
Trans-Activators
MHC class II
biology.protein
570 Life sciences
Original Article
Tumor necrosis factor alpha
Trans-Activators/ genetics
10244 Institute of Virology
medicine.drug
Zdroj: Journal of Experimental Medicine, Vol. 194, No 4 (2001) pp. 379-391
The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
Popis: Cell surface expression of major histocompatibility complex class II (MHCII) molecules is increased during the maturation of dendritic cells (DCs). This enhances their ability to present antigen and activate naive CD4+ T cells. In contrast to increased cell surface MHCII expression, de novo biosynthesis of MHCII mRNA is turned off during DC maturation. We show here that this is due to a remarkably rapid reduction in the synthesis of class II transactivator (CIITA) mRNA and protein. This reduction in CIITA expression occurs in human monocyte-derived DCs and mouse bone marrow–derived DCs, and is triggered by a variety of different maturation stimuli, including lipopolysaccharide, tumor necrosis factor α, CD40 ligand, interferon α, and infection with Salmonella typhimurium or Sendai virus. It is also observed in vivo in splenic DCs in acute myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalitis. The arrest in CIITA expression is the result of a transcriptional inactivation of the MHC2TA gene. This is mediated by a global repression mechanism implicating histone deacetylation over a large domain spanning the entire MHC2TA regulatory region.
Databáze: OpenAIRE
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