用编码泛素化乙型肝炎核心抗原的慢病毒载体修饰的树突细

StephenW

Mol Med Rep. 2018 Sep 14. doi: 10.3892/mmr.2018.9487. [Epub ahead of print]
Immunization with lentiviral vector‑modified dendritic cells encoding ubiquitinated hepatitis B core antigen promotes Th1 differentiation and antiviral immunity by enhancing p38 MAPK and JNK activation in HBV transgenic mice.
Dai S1, Chen X2, Yu Y2, Zang G2, Tang Z2.
Author information

1
    Department of Gastroenterology, Affiliated Renmin Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
2
    Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.

Abstract

Hepatitis B virus (HBV) infection is a global public health problem. T helper (Th)1‑associated cytokines are involved in HBV clearance during acute and persistent infection. In our previous study, it was demonstrated that lentiviral vectors encoding ubiquitinated hepatitis B core antigen (LV‑Ub‑HBcAg) effectively transduced dendritic cells (DCs) to induce maturation, which promoted T cell polarization to Th1 and generated HBcAg‑specific cytotoxic T lymphocytes (CTLs) ex vivo. In the present study, HBV transgenic mice were immunized with LV‑Ub‑HBcAg‑transduced DCs and HBcAg‑specific immune responses were evaluated. Cytokine expression was analyzed by ELISA. T lymphocyte proliferation was detected with a Cell Counting Kit‑8 assay and HBcAg‑specific CTL activity was determined using a lactate dehydrogenase release assay. The expression levels of p38‑mitogen‑activated protein kinase (p38‑MAPK), phosphorylated (p)‑p38MAPK, c‑Jun N‑terminal kinase (JNK) and p‑JNK were detected by western blot analysis. The results demonstrated that LV‑Ub‑HBcAg‑transduced DCs significantly increased the Th1/Th2 cytokine ratio, and effectively reduced the levels of serum hepatitis B surface antigen (HBsAg), HBV DNA, and liver HBsAg and HBcAg. Furthermore, the LV‑Ub‑HBcAg‑transduced DCs upregulated the expression of p‑P38‑MAPK and p‑JNK in T lymphocytes. In conclusion, the present study indicated that LV‑Ub‑HBcAg‑transduced DCs generated predominant Th1 responses and enhanced CTL activity in HBV transgenic mice. Activation of the P38‑MAPK/JNK signaling pathway may be involved in this induction.

PMID:
    30221736
DOI:
    10.3892/mmr.2018.9487

StephenW

Mol Med Rep.20188 Sep 14. doi：10.3892 / mmr.2018.9487。 [提前打印]
用编码泛素化乙型肝炎核心抗原的慢病毒载体修饰的树突细胞免疫通过增强HBV转基因小鼠中的p38MAPK和JNK活化来促进Th1分化和抗病毒免疫。
戴S1，陈X2，于亚2，臧G2，唐Z2。
作者信息

1
    江苏大学附属人民医院消化内科，江苏镇江212001，中国。
2
    上海交通大学附属第六人民医院传染病科，上海200233，中国。

抽象

乙型肝炎病毒（HBV）感染是一个全球性的公共卫生问题。 T辅助（Th）1相关细胞因子参与急性和持续感染期间的HBV清除。在我们之前的研究中，证明编码泛素化乙型肝炎核心抗原（LV-Ub-HBcAg）的慢病毒载体有效转导树突状细胞（DC）以诱导成熟，促进T细胞极化为Th1并产生HBcAg特异性细胞毒性T淋巴细胞。 （CTLs）离体。在本研究中，用LV-Ub-HBcAg转导的DC免疫HBV转基因小鼠，并评估HBcAg特异性免疫应答。通过ELISA分析细胞因子表达。用细胞计数试剂盒-8测定法检测T淋巴细胞增殖，并使用乳酸脱氢酶释放测定法测定HBcAg特异性CTL活性。通过蛋白质印迹分析检测p38-促分裂原活化蛋白激酶（p38-MAPK），磷酸化（p）-p38MAPK，c-Jun N-末端激酶（JNK）和p-JNK的表达水平。结果表明，LV-Ub-HBcAg转导的DC显着增加Th1 / Th2细胞因子比例，并有效降低血清乙型肝炎表面抗原（HBsAg），HBV DNA和肝脏HBsAg和HBcAg的水平。此外，LV-Ub-HBcAg转导的DC上调T淋巴细胞中p-P38-MAPK和p-JNK的表达。总之，本研究表明，LV-Ub-HBcAg转导的DC在HBV转基因小鼠中产生主要的Th1应答并增强CTL活性。 P38-MAPK / JNK信号传导途径的激活可能涉及该诱导。

结论：
    30221736
DOI：
    10.3892 / mmr.2018.9487