The ER membrane-anchored ubiquitin ligase Hrd1 is a positive regulator of T-cell immunity

Yuanming Xu, Fang Zhao, Quan Qiu, Kun Chen, Juncheng Wei, Qingfei Kong, Beixue Gao, Johanna Melo-Cardenas, Bin Zhang, Jinping Zhang, Jianxun Song, Donna D. Zhang, Jianing Zhang, Yunping Fan, Huabin Li*, Deyu Fang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Identification of positive regulators of T-cell immunity induced during autoimmune diseases is critical for developing novel therapies. The endoplasmic reticulum resident ubiquitin ligase Hrd1 has recently emerged as a critical regulator of dendritic cell antigen presentation, but its role in T-cell immunity is unknown. Here we show that genetic deletion of Hrd1 in mice inhibits T-cell proliferation, production of IL-2, and differentiation of Th1 and Th17 cells, and consequently protects mice from experimental autoimmune encephalomyelitis. Hrd1 facilitates T-cell proliferation by the destruction of cyclin-dependent kinase inhibitor p27 kip1, and deletion of p27 kip1 in Hrd1-null T-cells rescues proliferative capacity but not the production of cytokines, including IL-2, IFN-3 and IL-17. T-cell expression of Hrd1 is higher in patients with multiple sclerosis than in healthy individuals, and knockdown of Hrd1 in human CD4 + T cells inhibits activation and differentiation to Th1 and Th17 cells. Our study identifies Hrd1 as a previously unappreciated positive regulator of T cells and implies that Hrd1 is a potential therapeutic target for autoimmune diseases.

Original languageEnglish (US)
Article number12073
JournalNature communications
Volume7
DOIs
StatePublished - Jul 15 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'The ER membrane-anchored ubiquitin ligase Hrd1 is a positive regulator of T-cell immunity'. Together they form a unique fingerprint.

Cite this