Department of Hepatology, Yantai Qishan Hospital, Yantai, Shandong 264000, P.R. China.
Department of Oral and Maxillofacial Surgery, Yantai Stomatological Hospital, Yantai, Shandong 264000, P.R. China.
Mol Med Rep. 2023 Mar;27(3). doi: 10.3892/mmr.2023.12950. Epub 2023 Feb 3.
Hepatitis B virus (HBV) infection can activate macrophages to accelerate liver disease progression, including inflammation and fibrosis. However, the exact mechanism remains undetermined. The present study assessed the effects of macrophage polarization and the related cytokines on Th‑17 differentiation in HBeAg positive individuals with a HBV infection, and also evaluated the potential association of Th‑17 cell frequency with the severity of liver injury. A cross‑sectional study design was used to collect the clinical parameters, blood samples and liver tissue samples of patients with alanine transaminase £2x upper limit of normal and confirmed hepatitis B who underwent liver puncture in Qishan Hospital between January 2019‑December 2021. Macrophage and Th‑17 cell related factors were assayed using ELISA. The expression and quantification of cell surface antigen and intracellular markers in cells were assessed using flow cytometry. Pathological staining, including hematoxylin and eosin, reticular fiber staining and immunohistochemical staining were used to assess inflammation and fibrosis in the liver tissue. In the peripheral blood of patients with HBV infection, the number of CD14 macrophages was significantly increased compared with the healthy control, especially in the hepatitis B e antigen (HBeAg) positive group. CD14 macrophages were predominantly of the M1 type based on the assessment of the phenotype using flow cytometry and cytokine secretion. Furthermore, the percentage of M1 phenotype and related cytokines were positively correlated with Th‑17 differentiation. IL‑17A secreted by Th‑17 was positively correlated with the degree of liver inflammation and fibrosis, as well as with the severity of liver disease, which indicated that the differentiation of Th‑17 may be involved in the progression of liver disease. HBeAg may promote Th‑17 differentiation and IL‑17A production by M1 macrophages to accelerate the pathogenesis of liver inflammation and fibrosis in CHB patients.
乙型肝炎病毒（HBV）感染可激活巨噬细胞，加速肝脏疾病的进展，包括炎症和纤维化。然而，确切的机制仍未确定。本研究评估了巨噬细胞极化及其相关细胞因子对 HBeAg 阳性 HBV 感染者 Th17 分化的影响，并评估了 Th17 细胞频率与肝损伤严重程度的潜在关联。本研究采用横断面研究设计，收集了 2019 年 1 月至 2021 年 12 月期间在岐山医院接受肝穿刺的丙氨酸转氨酶 £2x 正常值上限且确诊为乙型肝炎的患者的临床参数、血液样本和肝组织样本。采用酶联免疫吸附试验测定巨噬细胞和 Th17 细胞相关因子。采用流式细胞术测定细胞表面抗原和细胞内标志物的表达和定量。采用苏木精和伊红、网状纤维染色和免疫组织化学染色对肝组织的炎症和纤维化进行病理染色。在 HBV 感染患者的外周血中，与健康对照组相比，CD14 巨噬细胞数量明显增加，尤其是在 HBeAg 阳性组。通过流式细胞术和细胞因子分泌评估表型，CD14 巨噬细胞主要为 M1 型。此外，M1 表型的百分比和相关细胞因子与 Th17 分化呈正相关。Th17 分泌的 IL-17A 与肝炎症和纤维化的程度以及肝病的严重程度呈正相关，表明 Th17 的分化可能参与了肝脏疾病的进展。HBeAg 可能通过 M1 巨噬细胞促进 Th17 分化和 IL-17A 的产生，从而加速 CHB 患者肝炎症和纤维化的发病机制。
