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      Clinical significance of changes in the Th17/Treg ratio in autoimmune liver disease

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          Abstract

          AIM

          To investigate the levels, ratios, and clinical significance of T helper 17 (Th17) cells and regulatory T (Treg) cells in the peripheral blood of patients with autoimmune liver disease (AILD).

          METHODS

          Forty-two AILD patients were included in the experimental group (group E), and 11 healthy subjects were recruited as the control group (group C). Flow cytometry was performed to determine the percentages of Th17 and Treg cells in peripheral blood lymphocytes. Furthermore, a range of biochemical indices was measured simultaneously in the blood of group E patients.

          RESULTS

          The percentage of Th17 cells and the Th17/Treg ratio were higher in group E than in group C ( P < 0.01), whereas the percentage of Tregs was lower in the group E patients ( P < 0.05). Patients in group E who were admitted with AILD in the active stage showed significantly higher Th17 percentages and Th17/Treg ratios than those measured in patients with AILD in remission ( P < 0.05). In addition, among patients with AILD in the active stage, individuals that remained unhealed after hospitalization showed significantly higher baseline values of the Th17 percentage and the Th17/Treg ratio than those detected in patients who improved after treatment ( P < 0.05). The results suggested that imbalance in the Th17/Treg ratio plays an important role in the pathogenesis and development of AILD.

          CONCLUSION

          A high Th17/Treg ratio appears to predict poor short-term prognosis in patients with AILD in the active stage.

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          EASL Clinical Practice Guidelines: Autoimmune hepatitis.

          (2015)
          Article 0 comments Cited 348 times – based on 0 reviews     Review now
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            IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis.

            Yutaka Komiyama, Susumu Nakae, Taizo Matsuki … (2006)
            IL-17 is a proinflammatory cytokine that activates T cells and other immune cells to produce a variety of cytokines, chemokines, and cell adhesion molecules. This cytokine is augmented in the sera and/or tissues of patients with contact dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL-17 is involved in the development of autoimmune arthritis and contact, delayed, and airway hypersensitivity in mice. As the expression of IL-17 is also augmented in multiple sclerosis, we examined the involvement of this cytokine in these diseases using IL-17(-/-) murine disease models. We found that the development of experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis, was significantly suppressed in IL-17(-/-) mice; these animals exhibited delayed onset, reduced maximum severity scores, ameliorated histological changes, and early recovery. T cell sensitization against myelin oligodendrocyte glycoprotein was reduced in IL-17(-/-) mice upon sensitization. The major producer of IL-17 upon treatment with myelin digodendrocyte glycopritein was CD4+ T cells rather than CD8+ T cells, and adoptive transfer of IL-17(-/-) CD4+ T cells inefficiently induced EAE in recipient mice. Notably, IL-17-producing T cells were increased in IFN-gamma(-/-) cells, while IFN-gamma-producing cells were increased in IL-17(-/-) cells, suggesting that IL-17 and IFN-gamma mutually regulate IFN-gamma and IL-17 production. These observations indicate that IL-17 rather than IFN-gamma plays a crucial role in the development of EAE.
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              Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease.

              Maria Longhi, Yun Tao Ma, Dimitrios Bogdanos … (2004)
              CD4(+) lymphocytes constitutively expressing the IL-2-receptor alpha-chain (CD25) regulate the activation of CD4 and CD8 autoreactive T-cells by suppressing their proliferation and effector function. The aim of this study is to: (1) measure the percentage of CD4(+)CD25(+) T-cells (T-regs) in patients with autoimmune liver disease at presentation and during remission, (2) correlate their frequency with disease activity, (3) determine their ability to expand and (4) to inhibit interferon-gamma (IFNgamma) production by CD4(+)CD25- T-cells. 41 patients were studied. Percentage of T-regs was determined on peripheral blood mononuclear cells (PBMCs) by triple-colour flow cytometry; their ability to expand by exposing PBMCs to a T-cell expander (CD3/CD28 Dynabeads); their immunoregulatory function by measuring their ability to suppress IFNgamma production by CD4(+)CD25(-) T-cells. T-regs were significantly less in patients than in controls, and at diagnosis than during remission. Their percentage was inversely correlated with titres of anti-liver kidney microsomal and soluble liver antigen autoantibodies. T-regs ability to expand was significantly lower in patients than in controls, but that to suppress IFNgamma production by CD4(+)CD25(-) T-cells was maintained. Decreased T-regs numbers and ability to expand may favour the emergence of liver-targeted autoimmunity, despite preserved suppressor function. Treatment should aim at increasing T-regs number.
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                Author and article information

                Journal
                Journal ID (nlm-ta): World J Gastroenterol
                Journal ID (iso-abbrev): World J. Gastroenterol
                Journal ID (publisher-id): WJG
                Title: World Journal of Gastroenterology
                Publisher: Baishideng Publishing Group Inc
                ISSN (Print): 1007-9327
                ISSN (Electronic): 2219-2840
                Publication date (Print): 7 June 2017
                Publication date (Electronic): 7 June 2017
                Volume: 23
                Issue: 21
                Pages: 3832-3838
                Affiliations
                Ting-Ting Feng, Ting Zou, Xin Wang, Wei-Feng Zhao, Ai-Lan Qin, Department of Infectious Diseases, the First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
                Author notes

                Author contributions: All authors contributed to this manuscript.

                Supported by the Tianqing Liver Disease Research Foundation, China Foundation for Hepatitis Prevention and Control, No. TQGB20150026; and Kejiaoxingwei Project of Suzhou, No. KJXW2016004.

                Correspondence to: Dr. Ai-Lan Qin, Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, 899 Pinghai Road Gusu District, Suzhou 215000, Jiangsu Province, China. cnailanqin@ 123456163.com

                Telephone: +86-512-67780365 Fax: +86-512-67780365

                Article
                Other ID: jWJG.v23.i21.pg3832
                DOI: 10.3748/wjg.v23.i21.3832
                PMC ID: 5467069
                PubMed ID: 28638223
                SO-VID: 2460995a-c2c2-4e11-a806-dd0eb8aeb27e
                Copyright © ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
                License:

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                Date received : 26 November 2016
                Date revision received : 21 February 2017
                Date accepted : 12 April 2017
                Categories
                Subject: Basic Study

                Keywords: autoimmune liver disease,helper t cell 17,regulatory t cells,short-term prognosis
                Data availability:
                Keywords: autoimmune liver disease, helper t cell 17, regulatory t cells, short-term prognosis

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