Inhibition of ERAP1 represses HLA-B27 free heavy chains expression on polarized macrophages and interrupts NK cells activation and function from ankylosing spondylitis
Copyright © 2023 Elsevier Inc. All rights reserved.
Publié dans: | Clinical immunology (Orlando, Fla.). - 1999. - 248(2023) vom: 20. März, Seite 109268 |
---|---|
Auteur principal: | |
Autres auteurs: | , , , , , , , , , , , , , |
Format: | Article en ligne |
Langue: | English |
Publié: |
2023
|
Accès à la collection: | Clinical immunology (Orlando, Fla.) |
Sujets: | Journal Article Research Support, Non-U.S. Gov't Ankylosing spondylitis Endoplasmic reticulum aminopeptidase 1 Free heavy chains Human leukocyte antigen-B27 Macrophage Natural killer cell HLA-B27 Antigen Minor Histocompatibility Antigens plus... |
Résumé: | Copyright © 2023 Elsevier Inc. All rights reserved. BACKGROUND: We aimed to assess if Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms might impress Human leukocyte antigen (HLA)-B27-free heavy chains (FHCs) expression on macrophages and eventually NK cell activation in Ankylosing spondylitis (AS) METHODS: Blood samples were obtained from 10 HLAB27+ patients with protective and 10 HLAB27+ patients with non-protective genotype. Monocytes were isolated and polarized toward M1 and M2 macrophages. ERAP1 was inhibited in macrophages, which were then co-cultured with autologous NK cells RESULTS: Expression of HLA-B27-FHCs on M1 and M2 macrophages was reduced in patients with protective ERAP1 genotype. Co-culturing ERAP1-inhibited M1 macrophages and NK cells from patients with protective genotype resulted in downmodulation of CD69 and CD107a markers on NK cells and reduced number of IFN-γ+ NK cells compared to that of patients with non-protective genotypes CONCLUSION: Inhibition of ERAP1 activity, by diminishing NK activation, may have therapeutic value in treating AS patients |
---|---|
Description: | Date Completed 14.03.2023 Date Revised 18.03.2023 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-7035 |
DOI: | 10.1016/j.clim.2023.109268 |