Interleukin-35 modulates the balance between viral specific CD4+CD25+CD127dim/- regulatory T cells and T helper 17 cells in chronic hepatitis B virus infection
Autor: | Lanlan Yang, Siqi Liu, Zhenjing Jin, Xue Shao, Qian Zhang, Jie Song, Shengnan Jia, Wudong Wang |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Adult Male T helper 17 cells Hepatitis B virus Adolescent chemical and pharmacologic phenomena Biology medicine.disease_cause T-Lymphocytes Regulatory Virus lcsh:Infectious and parasitic diseases 03 medical and health sciences Young Adult 0302 clinical medicine Hepatitis B Chronic RAR-related orphan receptor gamma Virology medicine Humans lcsh:RC109-216 IL-2 receptor Interleukin-7 receptor Interleukin-35 Research Interleukins Interleukin FOXP3 hemic and immune systems Regulatory T cells Interleukin-10 030104 developmental biology Infectious Diseases Interleukin 35 DNA Viral Th17 Cells 030211 gastroenterology & hepatology Female Immunosuppressive Agents |
Zdroj: | Virology Journal Virology Journal, Vol 16, Iss 1, Pp 1-10 (2019) |
ISSN: | 1743-422X |
Popis: | Background Interleukin (IL)-35 regulates imbalance between regulatory T cells (Tregs) and T helper (Th) 17 cells, leading to an important modulator in autoimmune disorder, cancer, and infectious diseases. Our previous study revealed an immunosuppressive activity of IL-35 in chronic hepatitis B virus (HBV) infection. Thus, the aim of the current study was to investigate the role of regulatory function of IL-35 to viral specific Tregs/Th17 cells balance in chronic HBV infection. Methods A total of 44 HLA-A2 restricted chronic HBV infected patients, including 21 of chronic hepatitis B (CHB) and 23 of asymptomatic HBV carriers (ASC) were enrolled. Purified CD4+ T cells or CD4+CD25+CD127dim/− Tregs were stimulated with recombinant IL-35. HBV core antigen specific Tregs and Th17 cells were determined by flow cytometry. FoxP3 and RORγt mRNA was measured by real-time PCR. Cytokines production (IL-10 and IL-17) was investigated by ELISA. Results Peripheral viral specific Tregs was comparable between CHB and ASC. However, increased percentage of viral specific Th17 cells was found in CHB, leading to the reduction of Tregs/Th17 ratio in CHB patients. IL-35 stimulation elevated viral specific Tregs, but not Th17 cells frequency, in both CHB and ASC, resulting in the elevation of Tregs/Th17 ratio in both groups. This process was accompanied by increased expression of FoxP3 mRNA and IL-10 production, and decreased IL-17 secretion and STAT3 phosphorylation in purified CD4+ T cells. Moreover, IL-35 stimulation inhibited viral specific Th17-like phenotype differentiation from Tregs in CHB patients. Effective anti-HBV therapy did not affect viral specific Tregs/Th17 cells frequency or IL-35 expression in CHB patients, however, reduced responsiveness of CD4+ T cells or Tregs to IL-35 stimulation in vitro. Conclusion Our findings indicated that IL-35 regulation to viral specific Tregs/Th17 balance may contribute to viral persistence in chronic HBV infection. |
Databáze: | OpenAIRE |
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