Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 14155, Iran.
Rheumatology Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Immunol Res. 2023 Oct;71(5):698-708. doi: 10.1007/s12026-023-09380-6. Epub 2023 Apr 25.
SLE is a multisystem autoimmune disease characterized by multiple immunological abnormalities including production of autoantibodies. While the etiology of SLE is largely unknown, it is generally accepted that both genetic and environmental factors contribute to disease risk and immune dysregulation. Production of IFN-α is important for protecting the host against infections; however, over stimulation of innate immune pathways can induce autoimmune disease. Environmental factors, particularly Epstein-Barr virus (EBV), have been proposed to play an important role in SLE disease. Improper engagement of Toll-like receptor (TLR) pathways by endogenous or exogenous ligands may lead to the initiation of autoimmune responses and tissue injury. EBV is shown to be a potent stimulant of IFN-α by TLR signaling cascades. Given the highlighted role of IFN-α in SLE pathogenesis and potential role of EBV infection in this disease, the present study is aimed at exploring the in vitro effects of EBV infection and CPG (either alone or in combination) on IFN-α. We also examined the expression level of CD20 and BDCA-4 and CD123 in PBMCs in 32 SLE patients and 32 healthy controls. Our results showed PBMCs treated with CPG-induced higher levels of IFN-α and TLR-9 gene expression fold change compared to cells treated with either EBV or EBV-CPG. Moreover, PBMCs treated with CPG produced significantly higher IFN-α concentration in supernatant compared to cells treated with EBV but not EBV-CPG. Our results further highlight the potential role of EBV infection and TLRs in SLE patients although more studies are warranted to ascertain the global imprint that EBV infection can have on immune signature in patients with SLE.
SLE 是一种多系统自身免疫性疾病，其特征为多种免疫异常，包括自身抗体的产生。虽然 SLE 的病因在很大程度上尚不清楚，但人们普遍认为遗传和环境因素均与疾病风险和免疫失调有关。IFN-α 的产生对于宿主抵抗感染至关重要；然而，固有免疫途径的过度刺激可诱发自身免疫性疾病。环境因素，特别是 EBV，被认为在 SLE 发病机制中起重要作用。内源性或外源性配体对 Toll 样受体（TLR）途径的不当结合可能导致自身免疫反应和组织损伤的发生。EBV 通过 TLR 信号级联反应被证明是 IFN-α 的有效刺激物。鉴于 IFN-α 在 SLE 发病机制中的突出作用以及 EBV 感染在该疾病中的潜在作用，本研究旨在探索 EBV 感染和 CPG（单独或联合）对 IFN-α 的体外作用。我们还检测了 32 例 SLE 患者和 32 例健康对照者 PBMCs 中 CD20 和 BDCA-4 及 CD123 的表达水平。结果显示，与单独用 EBV 或 EBV-CPG 处理的细胞相比，用 CPG 处理的 PBMCs 诱导产生更高水平的 IFN-α 和 TLR-9 基因表达倍数变化。此外，与用 EBV 处理的细胞相比，用 CPG 处理的 PBMCs 在培养上清中产生的 IFN-α 浓度显著更高，但与用 EBV-CPG 处理的细胞相比则没有显著差异。我们的结果进一步强调了 EBV 感染和 TLRs 在 SLE 患者中的潜在作用，尽管还需要更多的研究来确定 EBV 感染对 SLE 患者免疫特征的全面影响。
