ArticleJournal of innate immunity2015
Autoimmune disease-associated variants of extracellular endoplasmic reticulum aminopeptidase 1 induce altered innate immune responses by human immune cells.
Article in Journal of innate immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Review
- ERAP1 Activity Modulates the Immunopeptidome but Also Affects the Proteome, Metabolism, and Stress Responses in Cancer Cells.Molecular & cellular proteomics : MCP · 2025Article
- Decoding the inflammatory-osteogenic axis in ankylosing spondylitis: mechanisms, dysregulation, and emerging therapeutic interventions.Frontiers in immunology · 2025Review
- Association ofFrontiers in immunology · 2024Article
- Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions.Frontiers in cell and developmental biology · 2024Article
- Phosphinic Peptides as Tool Compounds for the Study of Pharmacologically Relevant Zn-Metalloproteases.ACS pharmacology & translational science · 2022Review
- Single-cell genome-wide association reveals that a nonsynonymous variant inCell genomics · 2022Article
- ERAP1 is a critical regulator of inflammasome-mediated proinflammatory and ER stress responses.BMC immunology · 2022Article
- Can ERAP1 and ERAP2 Form Functional Heterodimers? A Structural Dynamics Investigation.Frontiers in immunology · 2022Article
- Proteomic insight of seminal plasma in spinal cord injured men submitted to oral probenecid treatment for improved motility.The journal of spinal cord medicine · 2021Article
- ERAPs Reduce In Vitro HIV Infection by Activating Innate Immune Response.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19?International journal of molecular sciences · 2021Review
- The Potential Role of Genetics, Environmental Factors, and Gut Dysbiosis in the Aberrant Non-Coding RNA Expression to Mediate Inflammation and Osteoclastogenic/Osteogenic Differentiation in Ankylosing Spondylitis.Frontiers in cell and developmental biology · 2021Review
- ERAP, KIR, and HLA-C Profile in Recurrent Implantation Failure.Frontiers in immunology · 2021Article
- Paradoxical psoriasis induced by TNF-α blockade shows immunological features typical of the early phase of psoriasis development.The journal of pathology. Clinical research · 2020Article
- Molecular pathways for antigenic peptide generation by ER aminopeptidase 1.Molecular immunology · 2019Review
- Editing the immunopeptidome of melanoma cells using a potent inhibitor of endoplasmic reticulum aminopeptidase 1 (ERAP1).Cancer immunology, immunotherapy : CII · 2019Article
- ERAP1 allotypes shape the epitope repertoire of virus-specific CD8Journal of hepatology · 2019Article
- The role of polymorphic ERAP1 in autoinflammatory disease.Bioscience reports · 2018Review
- ERAP1 deficient mice have reduced Type 1 regulatory T cells and develop skeletal and intestinal features of Ankylosing Spondylitis.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms have been linked to several autoimmune diseases; however, the molecular mechanisms underlying these associations are not well understood. Recently, we demonstrated that ERAP1 regulates key aspects of the innate immune response. Previous studies show ERAP1 to be endoplasmic reticulum-localized and secreted during inflammation. Herein, we investigate the possible roles that ERAP1 polymorphic variants may have in modulating the innate immune responses of human peripheral blood mononuclear cells (hPBMCs) using two experimental methods: extracellular exposure of hPBMCs to ERAP1 variants and adenovirus (Ad)-based ERAP1 expression. We found that exposure of hPBMCs to ERAP1 variant proteins as well as ERAP1 overexpression by Ad5 vectors increased inflammatory cytokine and chemokine production, and enhanced immune cell activation. Investigating the molecular mechanisms behind these responses revealed that ERAP1 is able to activate innate immunity via multiple pathways, including the NLRP3 (NOD-like receptor, pyrin domain-containing 3) inflammasome. Importantly, these responses varied if autoimmune disease-associated variants of ERAP1 were examined in the assay systems. Unexpectedly, blocking ERAP1 cellular internalization augmented IL-1β production. To our knowledge, this is the first report identifying ERAP1 as being involved in modulating innate responses of human immune cells, a finding that may explain why ERAP1 has been genetically associated with several autoimmune diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.