PDF(Pubmed)
Abstract：
UNASSIGNED: Podocytes, as intrinsic renal cells, can also express MHC-II and costimulatory molecules under inflammatory conditions, suggesting that they may act as antigen-presenting cells (APCs) to activate immune cell responses and then lead to immune-mediated renal injury. They are already recognized as main targets in the pathogenic mechanism of hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN). Previous studies also have indicated that inflammatory cells infiltration and immune-mediated tissue injury are evident in the kidney samples of patients with HBV-GN. However, the role of podocytes immune disorder in the pathogenic mechanism of HBV-GN remains unclear.
UNASSIGNED: Renal function and inflammatory cells infiltration were measured in HBV transgenic (HBV-Tg) mice. In vitro, podocytes/CD4+ T cells or macrophages co-culture system was established. Then, the expression of HBx, CD4, and CD68 was determined by immunohistochemistry, while the expression of MHC-II, CD40, and CD40L was determined by immunofluorescence. Co-stimulatory molecules expression was examined by flow cytometry. The levels of inflammatory factors were detected by ELISA.
UNASSIGNED: In vivo, renal function was obviously impaired in HBV-Tg mice. HBx was significantly upregulated and immune cells infiltrated in the glomerulus of HBV-Tg mice. Expression of MHC-II and costimulatory molecule CD40 increased in the podocytes of HBV-Tg mice; CD4+ T cells exhibited increased CD40L expression in glomerulus. In vitro, CD40 expression was markedly elevated in HBx-podocytes. In co-culture systems, HBx-podocytes stimulated CD4+ T cells activation and caused the imbalance between IFN-γ and IL-4. HBx-podocytes also enhanced the adhesion ability of macrophages and induced the release of proinflammatory mediators.
UNASSIGNED: Taken together, these podocyte-related immune disorder may be involved in the pathogenic mechanism of HBV-GN.
UNASSIGNED: Renal function and inflammatory cells infiltration were measured in HBV transgenic (HBV-Tg) mice. In vitro, podocytes/CD4+ T cells or macrophages co-culture system was established. Then, the expression of HBx, CD4, and CD68 was determined by immunohistochemistry, while the expression of MHC-II, CD40, and CD40L was determined by immunofluorescence. Co-stimulatory molecules expression was examined by flow cytometry. The levels of inflammatory factors were detected by ELISA.
UNASSIGNED: In vivo, renal function was obviously impaired in HBV-Tg mice. HBx was significantly upregulated and immune cells infiltrated in the glomerulus of HBV-Tg mice. Expression of MHC-II and costimulatory molecule CD40 increased in the podocytes of HBV-Tg mice; CD4+ T cells exhibited increased CD40L expression in glomerulus. In vitro, CD40 expression was markedly elevated in HBx-podocytes. In co-culture systems, HBx-podocytes stimulated CD4+ T cells activation and caused the imbalance between IFN-γ and IL-4. HBx-podocytes also enhanced the adhesion ability of macrophages and induced the release of proinflammatory mediators.
UNASSIGNED: Taken together, these podocyte-related immune disorder may be involved in the pathogenic mechanism of HBV-GN.
摘要：
■足细胞，作为内在的肾细胞，还可以在炎症条件下表达MHC-II和共刺激分子，提示它们可能作为抗原呈递细胞（APC）激活免疫细胞反应，然后导致免疫介导的肾损伤。它们已经被认为是乙型肝炎病毒（HBV）相关性肾小球肾炎（HBV-GN）致病机制的主要靶标。先前的研究还表明，炎症细胞浸润和免疫介导的组织损伤在HBV-GN患者的肾脏样本中是明显的。然而,足细胞免疫紊乱在HBV-GN致病机制中的作用尚不清楚。
■在HBV转基因（HBV-Tg）小鼠中测量肾功能和炎性细胞浸润。体外，建立足细胞/CD4+T细胞或巨噬细胞共培养体系。然后，HBx的表达，通过免疫组织化学测定CD4和CD68，而MHC-II的表达，通过免疫荧光测定CD40和CD40L。通过流式细胞术检查共刺激分子的表达。ELISA法检测炎症因子水平。
■体内，HBV-Tg小鼠肾功能明显受损。HBV-Tg小鼠肾小球中HBx显著上调，免疫细胞浸润。MHC-II和共刺激分子CD40在HBV-Tg小鼠足细胞中的表达增加;CD4+T细胞在肾小球中表现出增加的CD40L表达。体外，CD40在HBx足细胞中表达显著升高。在共同文化系统中，HBx足细胞刺激CD4+T细胞活化并引起IFN-γ和IL-4之间的失衡。HBx足细胞还增强巨噬细胞的粘附能力并诱导促炎介质的释放。
■放在一起，这些与足细胞相关的免疫紊乱可能与HBV-GN的致病机制有关。
■在HBV转基因（HBV-Tg）小鼠中测量肾功能和炎性细胞浸润。体外，建立足细胞/CD4+T细胞或巨噬细胞共培养体系。然后，HBx的表达，通过免疫组织化学测定CD4和CD68，而MHC-II的表达，通过免疫荧光测定CD40和CD40L。通过流式细胞术检查共刺激分子的表达。ELISA法检测炎症因子水平。
■体内，HBV-Tg小鼠肾功能明显受损。HBV-Tg小鼠肾小球中HBx显著上调，免疫细胞浸润。MHC-II和共刺激分子CD40在HBV-Tg小鼠足细胞中的表达增加;CD4+T细胞在肾小球中表现出增加的CD40L表达。体外，CD40在HBx足细胞中表达显著升高。在共同文化系统中，HBx足细胞刺激CD4+T细胞活化并引起IFN-γ和IL-4之间的失衡。HBx足细胞还增强巨噬细胞的粘附能力并诱导促炎介质的释放。
■放在一起，这些与足细胞相关的免疫紊乱可能与HBV-GN的致病机制有关。
