Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection
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Journal of Translational Medicine Open Access
RESEARCH
Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection Xiaoyi Li1†, Qifan Zhang2†, Wanyue Zhang3, Guofu Ye1, Yanchen Ma1, Chunhua Wen1, Shuqin Gu1, Libo Tang1 and Yongyin Li1*
Abstract Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and C D19+ B cells. Results: We observed that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared to that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, positive correlations were observed between the frequencies of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and C XCR5+CD8+ T cells. Notably, in vitro experimental results demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic C D4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells. Conclusions: Expanded FDCs in patients with chronic HBV infection may favor host immune responses against HBV. The identification of this unique population of cell may contribute to a better understanding of the immune regulatory mechanisms associated with chronic HBV infection and provide a potential immunotherapeutic target for this disease. Keywords: Follicular dendritic cells, Hepatitis B virus, B cells, T cells
*Correspondence: [email protected] † Xiaoyi Li and Qifan Zhang share co-first authorship 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, No. 1838 North Guangzhou Avenue, Guangzhou 510515, China Full list of author information is available at the end of the article
Background Chronic hepatitis B virus (HBV) infection is a major global health burden and may lead to progressive liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). As current antiviral therapies primarily inhibit HBV DNA replication by targeting the process of reverse transcription and have no direct effects on covalently closed circular DNA (cccDNA), chronic hepatitis B (CHB) patients tend to relapse after drug withdrawal [1–4]. Therefore, the restoration
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