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The role of polymorphic ERAP1 in autoinflammatory disease

The role of polymorphic ERAP1 in autoinflammatory disease
The role of polymorphic ERAP1 in autoinflammatory disease

Autoimmune and autoinflammatory conditions represent a group of disorders characterized by self-directed tissue damage due to aberrant changes in innate and adaptive immune responses. These disorders possess widely varying clinical phenotypes and etiology; however, they share a number of similarities in genetic associations and environmental influences. Whilst the pathogenic mechanisms of disease remain poorly understood, genome wide association studies (GWAS) have implicated a number of genetic loci that are shared between several autoimmune and autoinflammatory conditions. Association of particular HLA alleles with disease susceptibility represents one of the strongest genetic associations. Furthermore, recent GWAS findings reveal strong associations with single nucleotide polymorphisms in the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene and susceptibility to a number of these HLA-associated conditions. ERAP1 plays a major role in regulating the repertoire of peptides presented on HLA class I alleles at the cell surface, with the presence of single nucleotide polymorphisms in ERAP1 having a significant impact on peptide processing function and the repertoire of peptides presented. The impact of this dysfunctional peptide generation on CD8+ T-cell responses has been proposed as a mechanism of pathogenesis diseases where HLA and ERAP1 are associated. More recently, studies have highlighted a role for ERAP1 in innate immune-mediated pathways involved in inflammatory responses. Here, we discuss the role of polymorphic ERAP1 in various immune cell functions, and in the context of autoimmune and autoinflammatory disease pathogenesis.

0144-8463
Reeves, Emma
bd61ff0c-6555-47fd-884f-74dc6105e846
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Reeves, Emma
bd61ff0c-6555-47fd-884f-74dc6105e846
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4

Reeves, Emma and James, Edward (2018) The role of polymorphic ERAP1 in autoinflammatory disease. Bioscience Reports, 38 (4), [BSR20171503]. (doi:10.1042/BSR20171503).

Record type: Review

Abstract

Autoimmune and autoinflammatory conditions represent a group of disorders characterized by self-directed tissue damage due to aberrant changes in innate and adaptive immune responses. These disorders possess widely varying clinical phenotypes and etiology; however, they share a number of similarities in genetic associations and environmental influences. Whilst the pathogenic mechanisms of disease remain poorly understood, genome wide association studies (GWAS) have implicated a number of genetic loci that are shared between several autoimmune and autoinflammatory conditions. Association of particular HLA alleles with disease susceptibility represents one of the strongest genetic associations. Furthermore, recent GWAS findings reveal strong associations with single nucleotide polymorphisms in the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene and susceptibility to a number of these HLA-associated conditions. ERAP1 plays a major role in regulating the repertoire of peptides presented on HLA class I alleles at the cell surface, with the presence of single nucleotide polymorphisms in ERAP1 having a significant impact on peptide processing function and the repertoire of peptides presented. The impact of this dysfunctional peptide generation on CD8+ T-cell responses has been proposed as a mechanism of pathogenesis diseases where HLA and ERAP1 are associated. More recently, studies have highlighted a role for ERAP1 in innate immune-mediated pathways involved in inflammatory responses. Here, we discuss the role of polymorphic ERAP1 in various immune cell functions, and in the context of autoimmune and autoinflammatory disease pathogenesis.

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More information

Accepted/In Press date: 23 July 2018
e-pub ahead of print date: 29 August 2018

Identifiers

Local EPrints ID: 424204
URI: http://eprints.soton.ac.uk/id/eprint/424204
ISSN: 0144-8463
PURE UUID: f3ac0da7-84f5-4978-bb08-cf2ee94d45c0
ORCID for Edward James: ORCID iD orcid.org/0000-0001-8638-7928

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Date deposited: 05 Oct 2018 11:34
Last modified: 22 Nov 2021 02:54

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Contributors

Author: Emma Reeves
Author: Edward James ORCID iD

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