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Published on: January 7, 2019
Inhibition of ERAP1 represses HLA-B27 free heavy chains expression on polarized macrophages and interrupts NK cells
Farhad Babaie1, Hamed Mohammadi2, Sorayya Salimi3
1Cellular 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.
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.
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