ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Proteasome immunosubunits protect against the development of CD8 T cell-mediated autoimmune diseases.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis.Journal of translational medicine · 2025Pooled it
- Trial
- Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes.PloS one · 2012Trial
- The role of immunoproteasome in diabetes and diabetes-related complications.Genes & diseases · 2026Review
- Effects of immunoproteasome inhibition on acute respiratory infection with murine hepatitis virus strain 1.Journal of virology · 2024Article
- Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits.PLoS biology · 2024Article
- Review
- Review
- Review
- Article
- Review
- Variations inInternational journal of general medicine · 2021Article
- Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum.Frontiers in immunology · 2021Review
- Identification of dynamic molecular networks in peripheral blood mononuclear cells in type 1 diabetes mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- Induction of Tolerance and Immunity by Dendritic Cells: Mechanisms and Clinical Applications.Frontiers in immunology · 2019Review
- Co-inhibition of immunoproteasome subunits LMP2 and LMP7 is required to block autoimmunity.EMBO reports · 2018Article
- The ubiquitin proteasome system as a potential therapeutic target for systemic sclerosis.Translational research : the journal of laboratory and clinical medicine · 2018Review
- Amelioration of autoimmunity with an inhibitor selectively targeting all active centres of the immunoproteasome.British journal of pharmacology · 2018Article
- Low Neurotoxicity of ONX-0914 Supports the Idea of Specific Immunoproteasome Inhibition as a Side-Effect-Limiting, Therapeutic Strategy.European journal of microbiology & immunology · 2017Article
- Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets.BMC genomics · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Exposure of cells to inflammatory cytokines induces the expression of three proteasome immunosubunits, two of which are encoded in the MHC class II region. The induced subunits replace their constitutive homologs in newly formed "so-called" immunoproteasomes. Immunosubunit incorporation enhances the proteasome's proteolytic activity and modifies the proteasome's cleavage-site preferences, which improves the generation of many MHC class I-presented peptides and shapes the fine specificity of pathogen-specific CD8 T cell responses. In this article, we report on a second effect of immunoproteasome formation on CD8 T cell responses. We show that mice deficient for the immunosubunits β5i/low molecular mass polypeptide (LMP7) and β2i/multicatalytic endopeptidase complex-like-1 develop early-stage multiorgan autoimmunity following irradiation and bone marrow transplantation. Disease symptoms are caused by CD8 T cells and are transferable into immunosubunit-deficient, RAG1-deficient mice. Moreover, using the human Type 1 Diabetes Genetics Consortium MHC dataset, we identified two single nucleotide polymorphisms within the β5i/LMP7-encoding gene sequences, which were in strong linkage disequilibrium, as independent genetic risk factors for type 1 diabetes development in humans. Strikingly, these single nucleotide polymorphisms significantly enhanced the risk conferred by HLA haplotypes that were previously shown to predispose for type 1 diabetes. These data suggested that inflammation-induced immunosubunit expression in peripheral tissues constitutes a mechanism that prevents the development of CD8 T cell-mediated autoimmune diseases.
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Registered trials
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