ArticlePloS one2013
Endoplasmic reticulum aminopeptidase-1 functions regulate key aspects of the innate immune response.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Differences between disease-associated endoplasmic reticulum aminopeptidase 1 (ERAP1) isoforms in cellular expression, interactions with tumour necrosis factor receptor 1 (TNF-R1) and regulation by cytokines.Clinical and experimental immunology · 2015Trial
- 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
- Identification of immunological patterns characterizing immune-related psoriasis reactions in oncological patients in therapy with anti-PD-1 checkpoint inhibitors.Frontiers in immunology · 2024Article
- Role of Endometrial Extracellular Vesicles in Mediating Cell-to-Cell Communication in the Uterus: A Review.Cells · 2023Review
- Paradoxical Effects of Endoplasmic Reticulum Aminopeptidase 1 Deficiency on HLA-B27 and Its Role as an Epistatic Modifier in Experimental Spondyloarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Markers of immune dysregulation in response to the ageing gut: insights from aged murine gut microbiota transplants.BMC gastroenterology · 2022Article
- Gene interaction analysis of psoriasis in Chinese Han population.Molecular genetics & genomic medicine · 2022Article
- ERAP1 is a critical regulator of inflammasome-mediated proinflammatory and ER stress responses.BMC immunology · 2022Article
- Multifactor dimensionality reduction reveals the effect of interaction between ERAP1 and IFIH1 polymorphisms in psoriasis susceptibility genes.Frontiers in genetics · 2022Article
- 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
- Impact of Natural OccurringInternational journal of molecular sciences · 2020Review
- Comprehensive analysis of circRNA expression profiles and circRNA-associated competing endogenous RNA networks in the development of mouse thymus.Journal of cellular and molecular medicine · 2020Article
- Review
- 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
- Unraveling the Molecular Signature of Extracellular Vesicles From Endometrial-Derived Mesenchymal Stem Cells: Potential Modulatory Effects and Therapeutic Applications.Frontiers in bioengineering and biotechnology · 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
- How ERAP1 and ERAP2 Shape the Peptidomes of Disease-Associated MHC-I Proteins.Frontiers in immunology · 2018Review
- Mice expressing human ERAP1 variants associated with ankylosing spondylitis have altered T-cell repertoires and NK cell functions, as well as increased in utero and perinatal mortality.International immunology · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum aminopeptidase-1 (ERAP1) is a multifunctional, ubiquitously expressed enzyme whose peptide-trimming role during antigen processing for presentation by MHC I molecules is well established, however, a role for ERAP1 in modulating global innate immune responses has not been described to date. Here we demonstrate that, relative to wild type mice, mice lacking ERAP1 exhibit exaggerated innate immune responses early during pathogen recognition, as characterized by increased activation of splenic and hepatic NK and NKT cells and enhanced production of pro-inflammatory cytokines such as IL12 and MCP1. Our data also revealed that ERAP1 is playing a critical role in NK cell development and function. We observed higher frequencies of terminally matured NK cells, as well as higher frequencies of licensed NK cells (expressing the Ly49C and Ly49I receptors) in ERAP1-KO mice, results that positively correlated with an enhanced NK activation and IFNγ production by ERAP1-KO mice challenged with pro-inflammatory stimuli. Furthermore, during pathogen recognition, ERAP1 regulates IL12 production by CD11c(+) DCs specifically, with increases in IL12 production positively correlated with an increased phagocytic activity of splenic DCs and macrophages. Collectively, our results demonstrate a previously unrecognized, more central role for the ERAP1 protein in modulating several aspects of both the development of the innate immune system, and its responses during the initial stages of pathogen recognition. Such a role may explain why ERAP1 has been implicated by GWAS in the pathogenesis of autoimmune diseases that may be precipitated by aberrant responses to pathogen encounters.
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Registered trials
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.