慢性乙型肝炎患者趋化因子CXCL13的升高表达与抗病毒治疗中

StephenW

Front Immunol. 2017 Mar 23;8:323. doi: 10.3389/fimmu.2017.00323. eCollection 2017.
Elevated Expression of Chemokine CXCL13 in Chronic Hepatitis B Patients Links to Immune Control during Antiviral Therapy.
Liu C1, Huang X1, Werner M2, Broering R2, Ge J1, Li Y1, Liao B3, Sun J1, Peng J1, Lu M4, Hou J1, Zhang X1.
Author information

1    State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University , Guangzhou , China.
2    Department of Gastroenterology and Hepatology, Essen University Hospital, University of Duisburg-Essen , Essen , Germany.
3    Department of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University , Guangzhou , China.
4    Institute of Virology, Essen University Hospital, University of Duisburg-Essen , Essen , Germany.

Abstract

C-X-C-chemokine ligand 13 (CXCL13), the ligand for C-X-C chemokine receptor type 5 (CXCR5), is a major regulator of B-cell trafficking and plays an integral role in age-dependent clearance of hepatitis B virus (HBV) in the mouse model. However, the expression and function of CXCL13 in patients with chronic hepatitis B (CHB) remain unknown. By use of liver cell subpopulations isolated from CHB patients, we found that CXCL13 mRNA was abundantly expressed in Kupffer cells (KCs), but not in primary hepatocytes, liver sinusoidal endothelial cells, and hepatic stellate cells. Interestingly, KC isolated from HBV-positive liver had much higher level of CXCL13 expression than non-HBV-infected controls. And its expression was induced by toll-like receptor 3 ligand poly I:C stimulation. Moreover, intense expression of CXCL13 protein and accumulation of CD4+ T and B cells were evident in follicular-like structures in the liver tissue of CHB patients, which indicated its chemotactic effect on CXCR5+ CD4+ cells and B cells. Consistently, the levels of serum CXCL13 were significantly higher in the CHB patients than in healthy controls. Furthermore, CXCL13 concentration was increased in the complete response (CR) group during weeks 0-12 and did not change significantly during the course of telbivudine treatment, compared with the patients who didn't achieve CR. In conclusion, the HBV-related increase of CXCL13 production in KC and serum CXCL13 level during telbivudine treatment might be associated with immune control of chronic HBV infection.
KEYWORDS:

CXCL13; Kupffer cell; chronic hepatitis B; hepatitis B virus; hepatitis B virus e antigen seroconversion

PMID:
    28386259
PMCID:
    PMC5362616
DOI:
    10.3389/fimmu.2017.00323

StephenW

前免疫2017年3月23日; 8：323。 doi：10.3389 / fimmu.2017.00323。 eCollection 2017。
慢性乙型肝炎患者趋化因子CXCL13的升高表达与抗病毒治疗中的免疫控制相关。
刘C1，黄X1，Werner M2，Broering R2，Ge J1，Li Y1，Liao B3，Sun J1，Peng J1，Lu M4，Hou J1，Zhang X1。
作者信息

1广东省南方医科大学南方医院传染病病毒性肝炎病毒性肝炎研究重点实验室器官功能衰竭研究国家重点实验室。
2德国埃森杜伊斯堡 - 埃森大学埃森大学医院消化内科和肝病学系。
3广州医科大学广州市第八人民医院传染病科，广州。
德国埃森杜伊斯堡 - 埃森大学埃森大学医院病毒学研究所。

抽象

CXC趋化因子配体13（CXCL13）是CXC趋化因子受体5型（CXCR5）的配体，是B细胞运输的主要调节因子，并且在小鼠的乙型肝炎病毒（HBV）的年龄依赖性清除中起着不可或缺的作用模型。然而，CXCL13在慢性乙型肝炎（CHB）患者中的表达和功能尚不清楚。通过使用从CHB患者分离的肝细胞亚群，我们发现CXCL13 mRNA在枯否细胞（KCs）中大量表达，但不是在原代肝细胞，肝窦内皮细胞和肝星状细胞中表达。有趣的是，从HBV阳性肝脏分离的KC的表达水平高于非HBV感染对照组。其表达由toll样受体3配体poly I：C刺激诱导。此外，CHB患者肝组织中CXCL13蛋白的强烈表达和CD4 + T和B细胞的积累在滤泡状结构中明显，表明其对CXCR5 + CD4 +细胞和B细胞的趋化作用。一致地，CHB患者血清CXCL13水平明显高于健康对照组。此外，在0-12周期间，完全缓解（CR）组的CXCL13浓度升高，在替比夫定治疗期间与未达到CR的患者相比，CXCL13浓度没有显着变化。总之，替比夫定治疗期间，CXCL13产生的KC和血清CXCL13水平的HBV相关性增加可能与慢性HBV感染的免疫控制有关。
关键词：

CXCL13;枯叶细胞慢性乙型肝炎乙型肝炎病毒;乙型肝炎病毒e抗原血清学转换

PMID：
    28386259
PMCID：
    PMC5362616
DOI：
    10.3389 / fimmu.2017.00323

StephenW

http://journal.frontiersin.org/a ... mmu.2017.00323/full