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Inhibition of Erap1 Represses Hla-B27 Free Heavy Chains Expression on Polarized Macrophages and Interrupts Nk Cells Activation and Function From Ankylosing Spondylitis Publisher Pubmed



Babaie F1, 2 ; Mohammadi H3, 4 ; Salimi S5, 6 ; Ghanavatinegad A7 ; Abbasifard M8, 9 ; Yousefi M10 ; Hajaliloo M11 ; Khalili Y12 ; Zamanlou S12 ; Safari R13 ; Hemmatzadeh M10 ; Rezaiemanesh A14 ; Salimi R15 ; Baradaran B5, 10 Show All Authors
Authors
  1. Babaie F1, 2
  2. Mohammadi H3, 4
  3. Salimi S5, 6
  4. Ghanavatinegad A7
  5. Abbasifard M8, 9
  6. Yousefi M10
  7. Hajaliloo M11
  8. Khalili Y12
  9. Zamanlou S12
  10. Safari R13
  11. Hemmatzadeh M10
  12. Rezaiemanesh A14
  13. Salimi R15
  14. Baradaran B5, 10
  15. Babaloo Z5, 10, 11
Show Affiliations
Authors Affiliations
  1. 1. Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
  2. 2. Department of Genetic and Immunology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  3. 3. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  4. 4. Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
  5. 5. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  6. 6. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  7. 7. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  9. 9. Department of Internal Medicine, Ali-Ibn Abi-Talib Hospital, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  10. 10. Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  11. 11. Connective Tissue Research Center, Tabriz University of Medical Science, Iran
  12. 12. Iranian Social Security Organization, Emam Reza Hospital, Urmia, Iran
  13. 13. Department of Infectious Disease, Imperial College London, London, United Kingdom
  14. 14. Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
  15. 15. Research and Development (R&D) Department, &RS Scientific, RS, Belgium

Source: Clinical Immunology Published:2023


Abstract

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 HLA[sbnd]B27+ patients with protective and 10 HLA[sbnd]B27+ 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. © 2023 Elsevier Inc.
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