The stimulator of interferon genes (STING) in macrophages plays a crucial role in nonalcoholic fatty liver disease (NAFLD) progression. However, there is a lack of evidence from large samples of patients to validate a deleterious role for STING in NAFLD. Moreover, sources of STING-expressing cells that are related to NAFLD remain to be definitively characterized. To investigate STING expression and explore its correlation with NAFLD progression in human subjects, our study involved liver samples from 98 NAFLD subjects and 8 controls. STING and p-TBK1 expression in nonparenchymal liver cells was analyzed and correlated with NAFLD pathological features. Numbers of STING⁺ cells were increased in livers from nonalcoholic steatohepatitis (NASH) patients compared with controls, especially in the liver portal tract of NASH patients with fibrosis (p < 0.05). Moreover, numbers of STING⁺ cells in livers of NASH patients were increased with aggravation of inflammation grade and fibrosis stage (p < 0.05). STING was mainly expressed in macrophages, including monocyte-derived macrophages (CCR2⁺, S100A9⁺), Kupffer cells (CD68⁺) and CD163⁺ macrophages. Compared with controls, numbers of STING⁺/CCR2⁺ and STING⁺/S100A9⁺ cells were significantly increased in livers from NASH patients with fibrosis and positively correlated with liver inflammation grade and fibrosis stage (p < 0.05). However, numbers of STING⁺/CD68⁺ and STING⁺/CD163⁺ cells were significantly increased in livers from NASH patients with advanced fibrosis and correlated only with aggravation of fibrosis stage (p < 0.05). Furthermore, compared with controls, NASH patients exhibited significantly increased STING⁺/p-TBK1⁺ cell numbers. In a coculture system, the amount of p-TBK1 and the mRNAs of IL1β and IL6 in THP1 macrophages, as well as the amount of α-SMA and the mRNAs of Col1a1, Fn and TGFβ1 in LX2 cells were significantly increased upon STING activation in macrophages (p < 0.05). Therefore, increased STING expression in MoMFs appears to be indicative of NAFLD progression, and STING could be a new target for NAFLD therapy.

巨噬细胞中的干扰素基因刺激物 (STING) 在非酒精性脂肪性肝病 (NAFLD) 的进展中起着至关重要的作用。然而，缺乏来自大量患者样本的证据来验证 STING 在 NAFLD 中的有害作用。此外，与 NAFLD 相关的表达 STING 的细胞的来源仍有待明确表征。为了研究 STING 表达并探索其与人类受试者 NAFLD 进展的相关性，我们的研究涉及来自 98 名 NAFLD 受试者和 8 名对照者的肝脏样本。分析了非实质肝细胞中的 STING 和 p-TBK1 表达，并将其与 NAFLD 病理特征相关联。STING 的数量⁺与对照组相比，非酒精性脂肪性肝炎 (NASH) 患者肝脏中的细胞增多，尤其是在伴有纤维化的 NASH 患者的肝门管中（p  < 0.05）。^{此外，随着炎症分级和纤维化分期的加重，NASH 患者肝脏中 STING +}细胞数量增加（p  < 0.05）。STING主要在巨噬细胞中表达，包括单核细胞来源的巨噬细胞（CCR2 ⁺、S100A9 ⁺）、Kupffer细胞（CD68 ⁺）和CD163 ⁺巨噬细胞。与对照相比，STING ⁺ /CCR2 ⁺和 STING ⁺ /S100A9 ⁺纤维化 NASH 患者肝脏中细胞显着增加，并且与肝脏炎症分级和纤维化分期呈正相关（p  < 0.05）。然而，晚期纤维化 NASH 患者肝脏中STING ⁺ /CD68 ⁺和 STING ⁺ /CD163 ⁺细胞数量显着增加，并且仅与纤维化阶段的加重相关（ p  < 0.05）。此外，与对照组相比，NASH 患者表现出显着增加的 STING ⁺ /p-TBK1 ⁺细胞数。在共培养系统中，STING 激活后，THP1 巨噬细胞中 p-TBK1 的量和 IL1β 和 IL6 的 mRNA 量，以及 LX2 细胞中 α-SMA 的量和 Col1a1、Fn 和 TGFβ1 的 mRNA 量显着增加巨噬细胞 ( p  < 0.05)。因此，MoMFs 中 STING 表达增加似乎表明 NAFLD 进展，STING 可能成为 NAFLD 治疗的新靶点。