Header

UZH-Logo

Maintenance Infos

Maturation of dendritic cells is accompanied by rapid transcriptional silencing of class II transactivator (Ciita) expression


LeibundGut-Landmann, Salomé; Mühlethaler-Mottet, Annick; Bernasconi, Luca; Suter, Tobias; Waldburger, Jean-Marc; Masternak, Krzysztof; Arrighi, Jean-François; Hauser, Conrad; Fontana, Adriano; Reith, Walter (2001). Maturation of dendritic cells is accompanied by rapid transcriptional silencing of class II transactivator (Ciita) expression. Journal of Experimental Medicine, 194(4):379-391.

Abstract

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 alpha, CD40 ligand, interferon alpha, 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.

Abstract

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 alpha, CD40 ligand, interferon alpha, 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.

Statistics

Citations

Dimensions.ai Metrics
133 citations in Web of Science®
134 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

17 downloads since deposited on 04 Jul 2019
6 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Virology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Language:English
Date:20 August 2001
Deposited On:04 Jul 2019 11:48
Last Modified:31 Jul 2020 03:27
Publisher:Rockefeller University Press
ISSN:0022-1007
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1084/jem.194.4.379
PubMed ID:11514596

Download

Hybrid Open Access

Download PDF  'Maturation of dendritic cells is accompanied by rapid transcriptional silencing of class II transactivator (Ciita) expression'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 433kB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)