ERAP1的抑制可抑制极化巨噬细胞上HLA - B27游离重链的表达，并阻断强直性脊柱炎患者NK细胞的激活和功能。
Inhibition of ERAP1 represses HLA-B27 free heavy chains expression on polarized macrophages and interrupts NK cells activation and function from ankylosing spondylitis.
作者信息
Babaie Farhad, Mohammadi Hamed, Salimi Sorayya, Ghanavatinegad Alireza, Abbasifard Mitra, Yousefi Mehdi, Hajaliloo Mehrzad, Khalili Younes, Zamanlou Sajjad, Safari Roghaiyeh, Hemmatzadeh Maryam, Rezaiemanesh Alireza, Salimi Reza, Baradaran Behzad, Babaloo Zohreh
机构信息
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.
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.
出版信息
Clin Immunol. 2023 Mar;248:109268. doi: 10.1016/j.clim.2023.109268. Epub 2023 Feb 16.
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.
背景
我们旨在评估内质网氨肽酶1（ERAP1）基因多态性是否会影响巨噬细胞上人类白细胞抗原（HLA）-B27游离重链（FHCs）的表达，并最终影响强直性脊柱炎（AS）患者自然杀伤细胞（NK细胞）的激活。
方法
从10例具有保护性基因型的HLA-B27患者和10例具有非保护性基因型的HLA-B27患者中采集血样。分离单核细胞并将其极化为M1和M2巨噬细胞。在巨噬细胞中抑制ERAP1，然后将其与自体NK细胞共培养。
结果
具有保护性ERAP1基因型的患者中，M1和M2巨噬细胞上HLA-B27-FHCs的表达降低。与具有非保护性基因型的患者相比，将来自具有保护性基因型患者的ERAP1抑制的M1巨噬细胞与NK细胞共培养，导致NK细胞上CD69和CD107a标志物下调，且IFN-γ NK细胞数量减少。
结论
抑制ERAP1活性，通过减少NK细胞激活，可能对治疗AS患者具有治疗价值。
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