Inhibition of ERAP1 represses HLA-B27 free heavy chains expression on polarized macrophages and interrupts NK cells activation and function from ankylosing spondylitis.

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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.
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