Reduced circulating interleukin 35 is associated with enhanced peripheral T cell function in primary biliary cholangitis

Authors

  • Siqi Liu Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin Province, China
  • Qian Zhang Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin Province, China
  • Mengyao Zhang Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin Province, China
  • Xuejing Zhong Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin Province, China
  • Wudong Wang Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin Province, China
  • Lishuang Wang Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin Province, China
  • Zhenjing Jin Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin Province, China https://orcid.org/0000-0002-2686-2907

DOI:

https://doi.org/10.17305/bjbms.2022.8147

Keywords:

Primary biliary cholangitis, interleukin 35, T lymphocites

Abstract

Interleukin 35 (IL-35) mediates immunosuppression of T cells in autoimmune diseases. T cells play an important role in primary biliary cholangitis (PBC) with incompletely elucidated pathogenesis. Thus, we aimed to investigate the role of IL-35 regulation on T cells in PBC patients. Fifty-one PBC patients and 28 controls were enrolled in this study. Plasma IL-35 level was measured. Purified peripheral CD4+ and CD8+ T cells were stimulated with exogenous IL-35 to investigate their functional phenotypes. IL-35-treated CD8+ T cells were cultured with human intrahepatic biliary epithelial cell line to determine the cytotoxicity of CD8+ T cells from PBC patients. Plasma IL-35 concentration was lower in PBC patients and negatively correlated with alkaline phosphatase. CD4+ T cells from PBC patients exhibited elevated transcription factor expressions and cytokine secretion, whereas CD8+ T cells produced increased cytotoxic molecules and cytokines. In vitro IL-35 stimulation suppressed the production of IL-17 and IL-22 by CD4+ T cells from PBC patients. CD8+ T cells treated with IL-35 mediated reduced target cell death in the direct contact co-culture system in PBC patients. This process was accompanied by reduced production of cytotoxic molecules and cytokines and increased expressions of immune checkpoint receptors in CD8+ T cells. Reduced circulating IL-35 might be insufficient to suppress T cell function, leading to the immune dysregulation in PBC patients.

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Reduced circulating interleukin 35 is associated with enhanced peripheral T cell function in primary biliary cholangitis

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Published

16-03-2023

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Section

Immunology

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How to Cite

1.
Reduced circulating interleukin 35 is associated with enhanced peripheral T cell function in primary biliary cholangitis. Biomol Biomed [Internet]. 2023 Mar. 16 [cited 2024 Apr. 25];23(2):248–258. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/8147