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Hrd1-mediated BLIMP-1 ubiquitination promotes dendritic cell MHCII expression for CD4 T cell priming during inflammation

The ubiquitin pathway plays critical roles in antigen presentation. However, the ubiquitin ligases that regulate MHC gene transcription remain unidentified. We showed that the ubiquitin ligase Hrd1, expression of which is induced by Toll-like receptor (TLR) stimulation, is required for MHC-II but no...

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Autores principales: Yang, Heeyoung, Qiu, Quan, Gao, Beixue, Kong, Sinyi, Lin, Zhenghong, Fang, Deyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235642/
https://www.ncbi.nlm.nih.gov/pubmed/25366967
http://dx.doi.org/10.1084/jem.20140283
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author Yang, Heeyoung
Qiu, Quan
Gao, Beixue
Kong, Sinyi
Lin, Zhenghong
Fang, Deyu
author_facet Yang, Heeyoung
Qiu, Quan
Gao, Beixue
Kong, Sinyi
Lin, Zhenghong
Fang, Deyu
author_sort Yang, Heeyoung
collection PubMed
description The ubiquitin pathway plays critical roles in antigen presentation. However, the ubiquitin ligases that regulate MHC gene transcription remain unidentified. We showed that the ubiquitin ligase Hrd1, expression of which is induced by Toll-like receptor (TLR) stimulation, is required for MHC-II but not MHC-I transcription in dendritic cells (DCs). Targeted Hrd1 gene deletion in DCs diminished MHC-II expression. As a consequence, Hrd1-null DCs failed to prime CD4(+) T cells without affecting the activation of CD8(+) T cells. Hrd1 catalyzed ubiquitination and degradation of the transcriptional suppressor B lymphocyte–induced maturation protein 1 (BLIMP1) to promote MHC-II expression. Genetic suppression of Hrd1 function in DCs protected mice from myelin oligodendrocyte glycoprotein (MOG)–induced experimental autoimmune encephalomyelitis (EAE). We identified Hrd1-mediated BLIMP1 ubiquitination as a previously unknown mechanism in programming DC for CD4(+) T cell activation during inflammation.
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spelling pubmed-42356422015-05-17 Hrd1-mediated BLIMP-1 ubiquitination promotes dendritic cell MHCII expression for CD4 T cell priming during inflammation Yang, Heeyoung Qiu, Quan Gao, Beixue Kong, Sinyi Lin, Zhenghong Fang, Deyu J Exp Med Article The ubiquitin pathway plays critical roles in antigen presentation. However, the ubiquitin ligases that regulate MHC gene transcription remain unidentified. We showed that the ubiquitin ligase Hrd1, expression of which is induced by Toll-like receptor (TLR) stimulation, is required for MHC-II but not MHC-I transcription in dendritic cells (DCs). Targeted Hrd1 gene deletion in DCs diminished MHC-II expression. As a consequence, Hrd1-null DCs failed to prime CD4(+) T cells without affecting the activation of CD8(+) T cells. Hrd1 catalyzed ubiquitination and degradation of the transcriptional suppressor B lymphocyte–induced maturation protein 1 (BLIMP1) to promote MHC-II expression. Genetic suppression of Hrd1 function in DCs protected mice from myelin oligodendrocyte glycoprotein (MOG)–induced experimental autoimmune encephalomyelitis (EAE). We identified Hrd1-mediated BLIMP1 ubiquitination as a previously unknown mechanism in programming DC for CD4(+) T cell activation during inflammation. The Rockefeller University Press 2014-11-17 /pmc/articles/PMC4235642/ /pubmed/25366967 http://dx.doi.org/10.1084/jem.20140283 Text en © 2014 Yang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Yang, Heeyoung
Qiu, Quan
Gao, Beixue
Kong, Sinyi
Lin, Zhenghong
Fang, Deyu
Hrd1-mediated BLIMP-1 ubiquitination promotes dendritic cell MHCII expression for CD4 T cell priming during inflammation
title Hrd1-mediated BLIMP-1 ubiquitination promotes dendritic cell MHCII expression for CD4 T cell priming during inflammation
title_full Hrd1-mediated BLIMP-1 ubiquitination promotes dendritic cell MHCII expression for CD4 T cell priming during inflammation
title_fullStr Hrd1-mediated BLIMP-1 ubiquitination promotes dendritic cell MHCII expression for CD4 T cell priming during inflammation
title_full_unstemmed Hrd1-mediated BLIMP-1 ubiquitination promotes dendritic cell MHCII expression for CD4 T cell priming during inflammation
title_short Hrd1-mediated BLIMP-1 ubiquitination promotes dendritic cell MHCII expression for CD4 T cell priming during inflammation
title_sort hrd1-mediated blimp-1 ubiquitination promotes dendritic cell mhcii expression for cd4 t cell priming during inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235642/
https://www.ncbi.nlm.nih.gov/pubmed/25366967
http://dx.doi.org/10.1084/jem.20140283
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