Characterization of immune responses associated with ERAP-1 expression in HSV-induced Behçet's disease mouse model

Hye-Myung Ryu; S M Shamsul Islam; Hasan M Sayeed; Rahar Babita; Je Kyung Seong; Ho Lee; Seonghyang Sohn

doi:10.1016/j.clim.2023.109305

Characterization of immune responses associated with ERAP-1 expression in HSV-induced Behçet's disease mouse model

Clin Immunol. 2023 May:250:109305. doi: 10.1016/j.clim.2023.109305. Epub 2023 Mar 31.

Authors

Hye-Myung Ryu¹, S M Shamsul Islam², Hasan M Sayeed², Rahar Babita¹, Je Kyung Seong³, Ho Lee⁴, Seonghyang Sohn⁵

Affiliations

¹ Department of Microbiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
² Department of Biomedical Sciences, Ajou University, Suwon 16499, Republic of Korea.
³ Laboratory of Developmental Biology and Genomics, BK21 Plus Program for Advanced Veterinary Science and Research Institute for Veterinary Science, College of Veterinary Medicine, Korea Mouse Phenotyping Center, Seoul National University, Seoul 08826, Republic of Korea; Interdiscplinary Program for Bioinformatics, Seoul National University, Seoul 08826, Republic of Korea; Korea Mouse Phenotyping Center, Seoul National University, Seoul 08826, Republic of Korea.
⁴ Korea Mouse Phenotyping Center, Seoul National University, Seoul 08826, Republic of Korea; Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi 10408, Republic of Korea.
⁵ Department of Microbiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea; Department of Biomedical Sciences, Ajou University, Suwon 16499, Republic of Korea. Electronic address: sohnsh@ajou.ac.kr.

PMID: 37003592
DOI: 10.1016/j.clim.2023.109305

Abstract

Behçet's disease (BD) is a chronic multisystem inflammatory disorder. Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphism has been reported as a risk factor for BD. However, the immunological role of ERAP1 in BD remains unclear. Therefore, the purpose of this study was to investigate the immunological role of ERAP1 in BD using a mouse model. ERAP1 incomplete expressing mice (ERAP1 hetero, +/-) were generated and inoculated with herpes simplex virus 1 to produce a BD mouse model. In these mice, dendritic cell activation markers and other immune response-related markers were analyzed. Among them, the factor showing a significant difference between ERAP1+/- BD mice and WT BD mice was IL-17. In ERAP1+/-, BD had significantly different expression levels of CD80, CD11b, Ly6G, RORγt, IFNγ, and IL-17 compared to asymptomatic controls. This study demonstrates ERAP1 defective expressions play an important role in BD development through inappropriate regulation of Th17.

Keywords: Behçet's disease; Dendritic cell; ERAP1; HSV; Th17.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminopeptidases / genetics
Behcet Syndrome* / genetics
Herpesvirus 1, Human*
Humans
Immunity
Interleukin-17 / genetics
Minor Histocompatibility Antigens / genetics
Risk Factors

Substances

Aminopeptidases
ERAP1 protein, human
Interleukin-17
Minor Histocompatibility Antigens
ERAP1 protein, mouse