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Notch Signaling Modulates the Balance of Regulatory T Cells and T Helper 17 Cells in Patients with Chronic Hepatitis C.
DNA Cell Biol 2017; 36(4):311-320DC

Abstract

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.

Authors+Show Affiliations

1 Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University , Weihui, Xinxiang, China .2 Department of Infectious Diseases, The First Affiliated Hospital of Xinxiang Medical University , Weihui, Xinxiang, China .2 Department of Infectious Diseases, The First Affiliated Hospital of Xinxiang Medical University , Weihui, Xinxiang, China .2 Department of Infectious Diseases, The First Affiliated Hospital of Xinxiang Medical University , Weihui, Xinxiang, China .2 Department of Infectious Diseases, The First Affiliated Hospital of Xinxiang Medical University , Weihui, Xinxiang, China .2 Department of Infectious Diseases, The First Affiliated Hospital of Xinxiang Medical University , Weihui, Xinxiang, China .1 Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University , Weihui, Xinxiang, China .

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28157396

Citation

Qin, Lei, et al. "Notch Signaling Modulates the Balance of Regulatory T Cells and T Helper 17 Cells in Patients With Chronic Hepatitis C." DNA and Cell Biology, vol. 36, no. 4, 2017, pp. 311-320.
Qin L, Zhou YC, Wu HJ, et al. Notch Signaling Modulates the Balance of Regulatory T Cells and T Helper 17 Cells in Patients with Chronic Hepatitis C. DNA Cell Biol. 2017;36(4):311-320.
Qin, L., Zhou, Y. C., Wu, H. J., Zhuo, Y., Wang, Y. P., Si, C. Y., & Qin, Y. M. (2017). Notch Signaling Modulates the Balance of Regulatory T Cells and T Helper 17 Cells in Patients with Chronic Hepatitis C. DNA and Cell Biology, 36(4), pp. 311-320. doi:10.1089/dna.2016.3609.
Qin L, et al. Notch Signaling Modulates the Balance of Regulatory T Cells and T Helper 17 Cells in Patients With Chronic Hepatitis C. DNA Cell Biol. 2017;36(4):311-320. PubMed PMID: 28157396.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Notch Signaling Modulates the Balance of Regulatory T Cells and T Helper 17 Cells in Patients with Chronic Hepatitis C. AU - Qin,Lei, AU - Zhou,Yan-Cai, AU - Wu,Hong-Jie, AU - Zhuo,Ya, AU - Wang,Yan-Ping, AU - Si,Chang-Yun, AU - Qin,Yong-Mei, Y1 - 2017/02/03/ PY - 2017/2/6/pubmed PY - 2017/4/13/medline PY - 2017/2/4/entrez KW - Notch signaling KW - T helper 17 cells KW - hepatitis C virus KW - regulatory T cells KW - viral persistence SP - 311 EP - 320 JF - DNA and cell biology JO - DNA Cell Biol. VL - 36 IS - 4 N2 - 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. SN - 1557-7430 UR - https://www.unboundmedicine.com/medline/citation/28157396/Notch_Signaling_Modulates_the_Balance_of_Regulatory_T_Cells_and_T_Helper_17_Cells_in_Patients_with_Chronic_Hepatitis_C_ L2 - https://www.liebertpub.com/doi/full/10.1089/dna.2016.3609?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -