Expression and Significance of Th17 Cells and Related Factors in Patients with Autoimmune Hepatitis

Author(s): Jihong An*.

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 22 , Issue 4 , 2019

Become EABM
Become Reviewer

Abstract:

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH).

Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry.

Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels.

Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.

Keywords: Th17 cells, IL-17, TNF-α, autoimmune hepatitis, liver damage, Asia-pacific region.

[1]
Sahebjam, F.; Vierling, J.M. Autoimmune hepatitis. Front. Med., 2015, 9(2), 187-219.
[2]
Aizawa, Y.; Hokari, A. Autoimmune hepatitis: Current challenges and future prospects. Clin. Exp. Gastroenterol., 2017, 10, 9-18.
[3]
Heneghan, M.A.; Yeoman, A.D.; Verma, S.; Smith, A.D.; Longhi, M.S. Autoimmune hepatitis. Lancet, 2013, 382(9902), 1433-1444.
[4]
Lapierre, P.; Beland, K.; Alvarez, F. Pathogenesis of autoimmune hepatitis: From break of tolerance to immune-mediated hepatocyte apoptosis. Transl. Res., 2007, 149(3), 107-113.
[5]
Manns, M.P.; Czaja, A.J.; Gorham, J.D.; Krawitt, E.L.; Mieli-Vergani, G.; Vergani, D.; Vierling, J.M. American Association for the Study of Liver Diseases.Diagnosis and management of autoimmune hepatitis. Hepatology, 2010, 51(6), 2193-2213.
[6]
European Association for the Study of the,L. EASL Clinical Practice Guidelines: Autoimmune hepatitis. J. Hepatol., 2015, 63(4), 971-1004.
[7]
Lapierre, P.; Béland, K.; Martin, C.; Alvarez, F., Jr; Alvarez, F. Forkhead box p3+ regulatory T cell underlies male resistance to experimental type 2 autoimmune hepatitis. Hepatology, 2010, 51(5), 1789-1798.
[8]
Shapiro, M.F.; Lehman, A.F. The diagnosis of depression in different clinical settings. An analysis of the literature on the dexamethasone suppression test. J. Nerv. Ment. Dis., 1983, 171(12), 714-720.
[9]
Rizvi, S.; Gawrieh, S. Autoimmune hepatitis in the elderly: Diagnosis and pharmacologic Management. Drugs Aging, 2018, 35(7), 589-602.
[10]
Qu, N.; Xu, M.; Mizoguchi, I.; Furusawa, J.; Kaneko, K.; Watanabe, K.; Mizuguchi, J.; Itoh, M.; Kawakami, Y.; Yoshimoto, T. Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in inflammatory diseases. Clin. Dev. Immunol., 2013, 2013, 968549.
[11]
Awasthi, A.; Kuchroo, V.K. Th17 cells: From precursors to players in inflammation and infection. Int. Immunol., 2009, 21(5), 489-498.
[12]
Fouser, L.A.; Wright, J.F.; Dunussi-Joannopoulos, K.; Collins, M. Th17 cytokines and their emerging roles in inflammation and autoimmunity. Immunol. Rev., 2008, 226, 87-102.
[13]
Yang, J.; Sundrud, M.S.; Skepner, J.; Yamagata, T. Targeting Th17 cells in autoimmune diseases. Trends Pharmacol. Sci., 2014, 35(10), 493-500.
[14]
Grant, C.R.; Liberal, R.; Holder, B.S.; Cardone, J.; Ma, Y.; Robson, S.C.; Mieli-Vergani, G.; Vergani, D.; Longhi, M.S. Dysfunctional CD39(POS) regulatory T cells and aberrant control of T-helper type 17 cells in autoimmune hepatitis. Hepatology, 2014, 59(3), 1007-1015.
[15]
Liang, M.; Liwen, Z.; Yun, Z.; Yanbo, D.; Jianping, C. The imbalance between Foxp3(+)Tregs and Th1/Th17/Th22 cells in patients with newly diagnosed autoimmune hepatitis. J. Immunol. Res., 2018, 2018, 3753081.
[16]
Muratori, L.; Longhi, M.S. The interplay between regulatory and effector T cells in autoimmune hepatitis: Implications for innovative treatment strategies. J. Autoimmun., 2013, 46, 74-80.
[17]
Wang, Q.X.; Yan, L.; Ma, X. Autoimmune hepatitis in the Asia-Pacific Area. J. Clin. Transl. Hepatol., 2018, 6(1), 48-56.
[18]
Vierling, J.M. Diagnosis and treatment of autoimmune hepatitis. Curr. Gastroenterol. Rep., 2012, 14(1), 25-36.
[19]
Brembilla, N.C.; Senra, L.; Boehncke, W.H. The IL-17 Family of cytokines in psoriasis: IL-17A and beyond. Front. Immunol., 2018, 9, 1682.
[20]
Longhi, M.S.; Liberal, R.; Holder, B.; Robson, S.C.; Ma, Y.; Mieli-Vergani, G.; Vergani, D. Inhibition of interleukin-17 promotes differentiation of CD25(-) cells into stable T regulatory cells in patients with autoimmune hepatitis. Gastroenterology, 2012, 142(7), 1526-1535. e6
[21]
John, K.; Hardtke-Wolenski, M.; Jaeckel, E.; Manns, M.P.; Schulze-Osthoff, K.; Bantel, H. Increased apoptosis of regulatory T cells in patients with active autoimmune hepatitis. Cell Death Dis., 2017, 8(12), 3219.
[22]
Zhao, L.; Tang, Y.; You, Z.; Wang, Q.; Liang, S.; Han, X.; Qiu, D.; Wei, J.; Liu, Y.; Shen, L.; Chen, X.; Peng, Y.; Li, Z.; Ma, X. Interleukin-17 contributes to the pathogenesis of autoimmune hepatitis through inducing hepatic interleukin-6 expression. PLoS One, 2011, 6(4), e18909.
[23]
Harada, K.; Shimoda, S.; Sato, Y.; Isse, K.; Ikeda, H.; Nakanuma, Y. Periductal interleukin-17 production in association with biliary innate immunity contributes to the pathogenesis of cholangiopathy in primary biliary cirrhosis. Clin. Exp. Immunol., 2009, 157(2), 261-270.
[24]
Lan, R.Y.; Salunga, T.L.; Tsuneyama, K.; Lian, Z.X.; Yang, G.X.; Hsu, W.; Moritoki, Y.; Ansari, A.A.; Kemper, C.; Price, J.; Atkinson, J.P.; Coppel, R.L.; Gershwin, M.E. Hepatic IL-17 responses in human and murine primary biliary cirrhosis. J. Autoimmun., 2009, 32(1), 43-51.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 22
ISSUE: 4
Year: 2019
Page: [232 - 237]
Pages: 6
DOI: 10.2174/1386207322666190402160455
Price: $65

Article Metrics

PDF: 23
HTML: 4