lncRNA‑CD160 decreases the immunity of CD8+ T cells through epigenetic mechanisms in hepatitis B virus infection

Wu,Jiansong; Niu,Qiang; Yuan,Jie; Xu,Xiaodan; Cao,Liuxia

doi:10.3892/ol.2020.11534

lncRNA‑CD160 decreases the immunity of CD8+ T cells through epigenetic mechanisms in hepatitis B virus infection

Authors:
- Jiansong Wu
- Qiang Niu
- Jie Yuan
- Xiaodan Xu
- Liuxia Cao
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Affiliations: Department of Infectious Diseases, General Hospital of the Peoples' Liberation Army Rocket Force, Beijing 100088, P.R. China
Published online on: April 15, 2020 https://doi.org/10.3892/ol.2020.11534
Pages: 235-247
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The transfer and development of chronic hepatitis B virus (HBV) infection is associated with the T cell immune response, therefore investigating the key regulators of cell immune response is needed to improve chronic HBV treatment. Blood samples from patients with chronic HBV infection were used to confirm the correlation between HBV infection stage and CD160 receptor expression levels in CD8+ T cells, the CD8+ T cells are used to research the mechanism of T cell immune response modulation, moreover, C3H/HeN mice with reduced CD160 expression levels were used to investigate the association between long non‑coding (lnc)RNA‑CD160 and HBV infection. Long non‑coding (lnc)RNA‑CD160 and histone‑modification enzyme gene histone deacetylase 11 (HDAC11) expression levels were negatively associated with CD160 expression. lncRNA‑CD160 can inhibit the secretion of IFN‑γ and TNF‑α through HDAC11 recruitment and bind to HDAC11 to form a complex on the promoters of IFN‑γ and TNF‑α. The HDAC11, IFN‑γ and TNF‑α form a complex and enhance the methylation of H3K9Me1, chromatin changes into the heterochromatin and the transcription of IFN‑γ and TNF‑α is blocked; moreover, the HDAC11/IFN‑γ/TNF‑α complex can also inhibit the secretion of IFN‑γ and TNF‑α in CD160‑ CD8+ T cells and suppresses the function of CD8+ T cells. Furthermore, small interfering RNA targeting lncRNA‑CD160 can block HBV infection progression. lncRNA‑CD160 acts as an immune suppressive factor and is expressed at a high level in peripheral blood CD8+ T cells of HBV infected patients. Furthermore, high expression levels of lncRNA‑CD160 can contribute to the inhibition of IFN‑γ and TNF‑α secretion in CD8+ T cells and decrease the immune response of CD8+ T cells. Therefore, lncRNA‑CD160 may become a new target for immunotherapy of chronic HBV infection in the future and may provide a new therapeutic strategy for the treatment of HBV infection.

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