Notch Signaling Modulates the Balance of Regulatory T Cells and T Helper 17 Cells in Patients with Chronic Hepatitis C
| Autor: | Lei Qin, Hong-Jie Wu, Yan-Cai Zhou, Yong-Mei Qin, Yan-Ping Wang, Ya Zhuo, Chang-Yun Si |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_treatment Hepatitis C virus Notch signaling pathway chemical and pharmacologic phenomena Biology medicine.disease_cause T-Lymphocytes Regulatory Peripheral blood mononuclear cell Young Adult 03 medical and health sciences Interleukin 21 0302 clinical medicine Downregulation and upregulation RAR-related orphan receptor gamma Genetics medicine Humans Receptor Notch2 Receptor Notch1 Molecular Biology Cells Cultured Cell Proliferation Interleukins Interleukin hemic and immune systems Cell Biology General Medicine Hepatitis C Chronic Middle Aged Nuclear Receptor Subfamily 1 Group F Member 3 030104 developmental biology Cytokine Immunology Th17 Cells Female Signal Transduction 030215 immunology |
| Zdroj: | DNA and Cell Biology. 36:311-320 |
| ISSN: | 1557-7430 1044-5498 |
| DOI: | 10.1089/dna.2016.3609 |
| Popis: | The imbalance of regulatory T cells (Tregs) and T helper 17 (Th17) cells contributes to the persistent hepatitis C virus (HCV) infection. However, modulatory factors associated with Tregs-Th17 balance were not fully elucidated. A recent study demonstrated an immunoregulatory strategy by inactivation of Notch signaling to reverse the disequilibrium of Tregs-Th17 cells in immune thrombocytopenia. Thus, the aim of this study was to assess the effect of Notch signaling in regulating the functions of Tregs and Th17 cells in chronic hepatitis C. A total of 46 patients with chronic hepatitis C and 17 normal controls (NCs) were enrolled. mRNA expressions of Notch1 and Notch2 were semiquantified by real-time reserve polymerase chain reaction. Percentages of Tregs-Th17, levels of key transcriptional factors, and cytokine productions were measured in response to treatment by DAPT, a γ-secretase inhibitor to suppress Notch signaling. We found that Notch1 and Notch2 mRNAs were significantly elevated in peripheral blood mononuclear cells from chronic hepatitis C patients compared with those from NCs. DAPT treatment reduced Th17 response by downregulation of RORγt expression and interleukin (IL)-17/IL-22 secretion. Tregs proportion, FoxP3 expression, and IL-10 production did not change significantly with DAPT treatment in chronic hepatitis C; however, blockage of Notch signaling inhibited the suppressive function of Tregs. Moreover, effective anti-HCV therapy not only reduced Notch1 and Notch2 expression but also decreased Tregs and Th17 proportions. The current data provided a novel mechanism underlying the modulation of Treg-Th17 balance. The link between Notch signaling and Th cells might lead to a new intervention for breaking immunotolerance of chronic HCV infection. |
| Databáze: | OpenAIRE |
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