Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis

Choi, Yoon Seok; Lee, Jeewon; Lee, Hyun Woong; Chang, Dong Yeop; Sung, Pil Soo; Jung, M.; Park, Jun Yong; Kim, Ja Kyung; Lee, Jung Il; Park, Hana; Cheong, Jae Youn; Suh, Kyung Suk; Kim, Hyung Joon; Lee, June Sung; Kim, Kyung-Ah; Shin, Eui‐Cheol

doi:10.1136/gutjnl-2013-306213

Cited by 41 publications

(35 citation statements)

References 43 publications

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“…A role for FOXP3 + T reg cells in the regulation of liver injury has been demonstrated in acute HAV infection. As described above, the number of T reg cells is decreased by FAS-mediated apoptosis during acute HAV infection; importantly, the number of T reg cells and the suppressive activity of the T reg cell population are inversely correlated with the degree of liver injury, which indicates that reduced suppressive activity of the T reg cell population results in severe liver injury during acute HAV infection 109 .…”

Section: Immunoregulatory Cellsmentioning

confidence: 92%

“…Delayed T cell responses during acute HCV infection may allow the virus more time to mutate and thus easily escape from the neutralizing activity of HCV E1-and E2-specific antibodies and from T cell recognition. In addition, the number of T reg cells tends to increase during acute HCV infection [98][99][100] , whereas these cells decrease during acute HAV infection 109 , which indicates that the larger T reg cell popu lation might contribute to the suppression of HCV-specific T cells in acute HCV infection. In summary, the characteristic immune responses that are elicited by HCV may explain why HCV infection often progresses to chronic persistent infection.…”

Section: Chronic Hepatitis Virus Infectionmentioning

confidence: 99%

“…During acute HAV infection, the frequency of T reg cells in the blood is decreased by FAS (also known as CD95)-mediated apoptosis 109 . In addition, the suppressive function of T reg cells can be directly inhibited by the binding of HAV particles to T reg cells through the immunoregulatory receptor TIM1 (also known as HAVCR1) 110 .…”

Section: Acute Hav Infectionmentioning

confidence: 99%

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Immune responses and immunopathology in acute and chronic viral hepatitis

2016

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Hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are responsible for most cases of viral hepatitis. Infection by each type of virus results in a different typical natural disease course and clinical outcome that are determined by virological and immunological factors. HCV tends to establish a chronic persistent infection, whereas HAV does not. HBV is effectively controlled in adults, although it persists for a lifetime after neonatal infection. In this Review, we discuss the similarities and differences in immune responses to and immunopathogenesis of HAV, HBV and HCV infections, which may explain the distinct courses and outcomes of each hepatitis virus infection.

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Section: Immunoregulatory Cellsmentioning

confidence: 92%

Section: Chronic Hepatitis Virus Infectionmentioning

confidence: 99%

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Immune responses and immunopathology in acute and chronic viral hepatitis

2016

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“…In the setting of acute liver injury, such as acute viral hepatitis A, the size of the Treg pool was contracted due to Treg apoptosis via a Fas-mediated mechanism (22). Hepatitis B (HBV) pathogenesis is immunologically mediated and increased frequencies of CD4 + CD25 high CD45RO + Treg and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) cells were noted in the peripheral blood of patients compared with controls and in patients who had recovered from a previous episode of HBV infection (23, 24).…”

Section: Profile Of Regulatory T Cells In Liver Diseasesmentioning

confidence: 99%

Clinical Potential of Regulatory T Cell Therapy in Liver Diseases: An Overview and Current Perspectives

et al. 2016

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The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg). The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis, or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients. Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment, and good manufacturing practice facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases (AILD), chronic rejection, and posttransplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases, and solid organ transplantations. There have not been any new therapies for the AILD for more than three decades; thus, the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior, and microenvironment of Treg before applying the cells to the patients.

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“…The T REG cell pool is depleted during HAV infection due to Fas-mediated cellular apoptosis, resulting in severe liver injury [48] . As well as acute HEV infection, superinfection with HAV also results in the development of ACLF [49] .…”

Section: Insult/injurymentioning

confidence: 99%

Acute-on-chronic liver failure: recent update

Alam

Suen

2016

J Biomed Res

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Acute on chronic liver failure (ACLF) was first described in 1995 as a clinical syndrome distinct to classic acute decompensation. Characterized by complications of decompensation, ACLF occurs on a background of chronic liver dysfunction and is associated with high rates of organ failure and significant short-term mortality estimated between 45% and 90%. Despite the clinical relevance of the condition, it still remains largely undefined with continued disagreement regarding its precise etiological factors, clinical course, prognostic criteria and management pathways. It is concerning that, despite our relative lack of understanding of the condition, the burden of ACLF among cirrhotic patients remains significant with an estimated prevalence of 30.9%. This paper highlights our current understanding of ACLF, including its etiology, diagnostic and prognostic criteria and pathophysiology. It is evident that further refinement of the ACLF classification system is required in order to detect high-risk patients and improve short-term mortality rates. The field of metabolomics certainly warrants investigation to enhance diagnostic and prognostic parameters, while the use of granulocyte-colony stimulating factor is a promising future therapeutic intervention for patients with ACLF.

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Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis

Abstract: The size of the Treg pool was contracted during AHA, resulting from apoptosis of Tregs induced by a Fas-mediated mechanism. Decrease in Treg numbers led to reduced suppressive activity of the Treg pool and consequently resulted in severe liver injury during AHA.

Cited by 41 publications

References 43 publications

Immune responses and immunopathology in acute and chronic viral hepatitis

Immune responses and immunopathology in acute and chronic viral hepatitis

Clinical Potential of Regulatory T Cell Therapy in Liver Diseases: An Overview and Current Perspectives

Acute-on-chronic liver failure: recent update

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