Inflammation drives an altered phenotype of mucosal-associated invariant T cells in chronic hepatitis D virus infection

Kefalakes, Helenie; Rehermann, Barbara

doi:10.1016/j.jhep.2019.05.024

Cited by 6 publications

(4 citation statements)

References 20 publications

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“…The frequency of MAIT cells was found to be reduced in the liver during chronic HCV infection but was improved within 4 weeks of therapy with DAA, with normalization of serum ALT activity. 115 Activation of MAIT cells in a TCRindependent but cytokine-dependent manner, such as IL-18 induced by HCV infection or interferon (IFN)-α for HCV treatment, led to cytokine release and granzyme B production, correlating with reduced HCV replication. 116 Patients with chronic HDV infection exhibited signs of microbial translocation in the liver and enhanced levels of IL-12 and IL-18, which induced activation of residual MAIT cells with a distinct phenotype (CD38 hi CD28 lo CD127 lo PD-1 hi ) and promoted MAIT cell apoptosis, leading to loss of intrahepatic MAIT cells.…”

Section: Viral Infectionmentioning

confidence: 99%

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Chen

Tian

2020

Cell Mol Immunol

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The liver is a lymphoid organ with unique immunological properties, particularly, its predominant innate immune system. The balance between immune tolerance and immune activity is critical to liver physiological functions and is responsible for the sensitivity of this organ to numerous diseases, including hepatotropic virus infection, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, and liver cancer, which are major health problems globally. In the past decade, with the discovery of liver-resident natural killer cells, the importance of innate lymphocytes with tissue residency has gradually become the focus of research. In this review, we address the current knowledge regarding hepatic innate lymphocytes with unique characteristics, including NK cells, ILC1/2/3s, NKT cells, γδ T cells, and MAIT cells, and their potential roles in liver homeostasis maintenance and the progression of liver diseases and cancer. A better understanding of the immunopathogenesis of hepatic innate lymphocytes will be helpful for proposing effective treatments for liver diseases and cancer.

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Section: Viral Infectionmentioning

confidence: 99%

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Chen

Tian

2020

Cell Mol Immunol

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“…In settings of chronic inflammation, infection or cancer, MAIT cells display altered phenotypes ( 112 ), can produce Th2 cytokines ( 113 ), and can contribute to pathology ( 114 ). MAIT cell function may be impaired in settings such as chronic infection ( 115 – 117 ) and cancer ( 118 ).…”

Section: The Context Of Antigen Recognition Determines Mait Cell Respmentioning

confidence: 99%

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

et al. 2020

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Mucosal-associated Invariant T (MAIT) cells recognize vitamin B-based antigens presented by the non-polymorphic MHC class I related-1 molecule (MR1). Both MAIT T cell receptors (TCR) and MR1 are highly conserved among mammals, suggesting an important, and conserved, immune function. For many years, the antigens they recognize were unknown. The discovery that MR1 presents vitamin B-based small molecule ligands resulted in a rapid expansion of research in this area, which has yielded information on the role of MAIT cells in immune protection, autoimmune disease and recently in homeostasis and cancer. More recently, we have begun to appreciate the diverse nature of the small molecule ligands that can bind MR1, with several less potent antigens and small molecule drugs that can bind MR1 being identified. Complementary structural information has revealed the complex nature of interactions defining antigen recognition. Additionally, we now view MAIT cells (defined here as MR1-riboflavin-Ag reactive, TRAV1-2 + cells) as one subset of a broader family of MR1-reactive T cells (MR1T cells). Despite these advances, we still lack a complete understanding of how MR1 ligands are generated, presented and recognized in vivo . The biological relevance of these MR1 ligands and the function of MR1T cells in infection and disease warrants further investigation with new tools and approaches.

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“…MAIT cells are unconventional innate‐like T cells, recognizing non‐peptide antigens presented by specialized monomorphic major histocompatibility class (MHC) I‐like molecules, termed MR1 91 . These T cells, usually have unique and conserved TCR repertoires, consisting of an invariant TCR α‐chain (Vα7.2) paired with a restricted TCR β‐chain repertoire and are typically identified by the C‐type lectin CD161, 92 although this marker can also be negative in more immature MAIT cells 93 . They are stimulated in a TCR‐independent manner by proinflammatory cytokines, such as IL12 and IL18, but also in a TCR‐dependent manner by bacterial metabolites of vitamin B, 94 which are presented by MR1.…”

Section: Innate Immune Responsementioning

confidence: 99%

Immunology of hepatitis D virus infection: General concepts and present evidence

Hoblos

Kefalakes

2022

Liver International

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Infection with the hepatitis D virus induces the most severe form of chronic viral hepatitis, affecting over 12 million people worldwide. Chronic HDV infection leads to rapid development of liver cirrhosis and hepatocellular carcinoma in ~70% of patients within 15 years of infection. Recent evidence suggests that an interplay of different components of the immune system are contributing to viral control and may even be implicated in liver disease pathogenesis. This review will describe general concepts of antiviral immune response and elicit the present evidence concerning the interplay of the hepatitis D virus with the immune system.

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Inflammation drives an altered phenotype of mucosal-associated invariant T cells in chronic hepatitis D virus infection

Cited by 6 publications

References 20 publications

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

Immunology of hepatitis D virus infection: General concepts and present evidence

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