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

Heeyoung Yang, Quan Qiu, Beixue Gao, Sinyi Kong, Zhenghong Lin, Deyu Fang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2467-2479
Number of pages13
JournalJournal of Experimental Medicine
Volume211
Issue number12
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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