PMID- 36804470
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20230318
IS  - 1521-7035 (Electronic)
IS  - 1521-6616 (Linking)
VI  - 248
DP  - 2023 Mar
TI  - Inhibition of ERAP1 represses HLA-B27 free heavy chains expression on polarized 
      macrophages and interrupts NK cells activation and function from ankylosing 
      spondylitis.
PG  - 109268
LID - S1521-6616(23)00047-5 [pii]
LID - 10.1016/j.clim.2023.109268 [doi]
AB  - 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-gamma(+) 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.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Babaie, Farhad
AU  - Babaie F
AD  - Cellular and Molecular Research Center, Cellular and Molecular Medicine 
      Institute, Urmia University of Medical Sciences, Urmia, Iran; Department of 
      Genetic and Immunology, Faculty of Medicine, Urmia University of Medical 
      Sciences, Urmia, Iran.
FAU - Mohammadi, Hamed
AU  - Mohammadi H
AD  - Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, 
      Karaj, Iran; Department of Immunology, School of Medicine, Alborz University of 
      Medical Sciences, Karaj, Iran.
FAU - Salimi, Sorayya
AU  - Salimi S
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 
      Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
FAU - Ghanavatinegad, Alireza
AU  - Ghanavatinegad A
AD  - Department of Immunology, School of Public Health, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Abbasifard, Mitra
AU  - Abbasifard M
AD  - Immunology of Infectious Diseases Research Center, Research Institute of Basic 
      Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; 
      Department of Internal Medicine, Ali-Ibn Abi-Talib Hospital, School of Medicine, 
      Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
FAU - Yousefi, Mehdi
AU  - Yousefi M
AD  - Department of Immunology, School of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Hajaliloo, Mehrzad
AU  - Hajaliloo M
AD  - Connective Tissue Research Center, Tabriz University of Medical Science, Iran.
FAU - Khalili, Younes
AU  - Khalili Y
AD  - Iranian Social Security Organization, Emam Reza Hospital, Urmia, Iran.
FAU - Zamanlou, Sajjad
AU  - Zamanlou S
AD  - Iranian Social Security Organization, Emam Reza Hospital, Urmia, Iran.
FAU - Safari, Roghaiyeh
AU  - Safari R
AD  - Department of Infectious Disease, Imperial College London, London, UK.
FAU - Hemmatzadeh, Maryam
AU  - Hemmatzadeh M
AD  - Department of Immunology, School of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Rezaiemanesh, Alireza
AU  - Rezaiemanesh A
AD  - Department of Immunology, School of Medicine, Kermanshah University of Medical 
      Sciences, Kermanshah, Iran.
FAU - Salimi, Reza
AU  - Salimi R
AD  - Research and Development (R&D) Department, RS, &RS Scientific, Belgium.
FAU - Baradaran, Behzad
AU  - Baradaran B
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 
      Department of Immunology, School of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran. Electronic address: baradaranb@tbzmed.ac.ir.
FAU - Babaloo, Zohreh
AU  - Babaloo Z
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 
      Department of Immunology, School of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran; Connective Tissue Research Center, Tabriz University of 
      Medical Science, Iran. Electronic address: zbabaloo@tbzmed.ac.ir.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230216
PL  - United States
TA  - Clin Immunol
JT  - Clinical immunology (Orlando, Fla.)
JID - 100883537
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - EC 3.4.11.- (ERAP1 protein, human)
RN  - EC 3.4.11.- (Aminopeptidases)
SB  - IM
MH  - Humans
MH  - *Spondylitis, Ankylosing/genetics
MH  - Polymorphism, Genetic
MH  - Genotype
MH  - Macrophages
MH  - Killer Cells, Natural
MH  - HLA-B27 Antigen/genetics/metabolism
MH  - Minor Histocompatibility Antigens
MH  - Polymorphism, Single Nucleotide
MH  - Genetic Predisposition to Disease
MH  - Aminopeptidases/genetics
OTO - NOTNLM
OT  - Ankylosing spondylitis
OT  - Endoplasmic reticulum aminopeptidase 1
OT  - Free heavy chains
OT  - Human leukocyte antigen-B27
OT  - Macrophage
OT  - Natural killer cell
COIS- Declaration of Competing Interest The authors declare that they have no conflict 
      of interest.
EDAT- 2023/02/23 06:00
MHDA- 2023/03/15 06:00
CRDT- 2023/02/22 08:45
PHST- 2022/07/31 00:00 [received]
PHST- 2023/01/27 00:00 [revised]
PHST- 2023/01/30 00:00 [accepted]
PHST- 2023/02/23 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/02/22 08:45 [entrez]
AID - S1521-6616(23)00047-5 [pii]
AID - 10.1016/j.clim.2023.109268 [doi]
PST - ppublish
SO  - Clin Immunol. 2023 Mar;248:109268. doi: 10.1016/j.clim.2023.109268. Epub 2023 Feb 
      16.