Endoplasmic Reticulum Aminopeptidase 1 beyond Antigenic Peptide-Processing Enzyme in the Endoplasmic Reticulum

Abstract

Endoplasmic reticulum aminopeptidase 1 (ERAP1) is well known as a processing enzyme of antigenic peptides, which are presented to major histocompatibility complex (MHC) class I molecules in the lumen of endoplasmic reticulum. Besides antigen processing, ERAP1 performs multiple functions in various cells depending on its intracellular and extracellular localization. Of note is the secretion of ERAP1 into the extracellular milieu in response to inflammatory stimuli, which further activates immune cells including macrophages and natural killer cells. Furthermore, secreted ERAP1 enhances the expression of pro-inflammatory cytokines like tumor necrosis factor-α, interleukin-1β, and interleukin-6. Such findings indicate that ERAP1 plays a significant role in the field of innate and acquired immunity. This review summarizes the functional analyses of ERAP1 that support our current understanding of its role as more than an antigenic peptideprocessing enzyme, specifically emphasizing on its secretory form.

Endoplasmic Reticulum Aminopeptidase 1 Is Involved in Anti-viral Immune Response of Hepatitis B Virus by Trimming Hepatitis B Core Antigen to Generate 9-Mers Peptides

“…Endoplasmic reticulum aminopeptidase 1 is usually retained in the lumen of ER and was therefore named for the localization. However, it could be secreted into the extracellular milieu in response to inflammatory stimuli, although the precise molecular mechanisms behind the secretion remain unclear ( Tsujimoto et al, 2020 ). We therefore analyzed peripheral ERAP1 level in patients with CHB.…”

Single-cell genome-wide association reveals that a nonsynonymous variant in ERAP1 confers increased susceptibility to influenza virus

“…This includes regulation of immune cell activation and cytokine production through secreted ERAP1. 77,78 However, scHi-HOST is a pooled infection assay and thus would not be expected to identify genetic differences that impact secreted factors acting through noncell-autonomous effects. ERAP1 also regulates ectodomain shedding of cell-surface receptors.…”

Single-cell genome-wide association reveals a nonsynonymous variant inERAP1confers increased susceptibility to influenza virus

“…Alternatively to affecting MHC-I presentation, ERAP1 has functions beyond MHC I peptide trimming that may contribute to its role in IAV infection. This includes regulation of immune cell activation and cytokine production through secreted ERAP1 (Aldhamen et al, 2015;Tsujimoto et al, 2020). However, scHi-HOST is a pooled infection assay, and thus would not be expected to identify genetic differences that impact secreted acting through non-cellautonomous effects.…”