Tissue-Resident Memory T Cells in the Liver—Unique Characteristics of Local Specialists

Bartsch, Lea M.; Damasio, Marcos; Subudhi, Sonu; Drescher, Hannah K.

doi:10.3390/cells9112457

Cited by 20 publications

(19 citation statements)

References 110 publications

(142 reference statements)

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“…Although many immunological insights into HBV pathogenesis have been made by studying peripheral blood, it has come to light that tissue-resident immune subsets play vital roles in front-line immunosurveillance in the liver 9 10. For example, the liver is enriched with mucosal-associated invariant T (MAIT) cells, natural killer (NK) cells, and unique tissue-resident CD8+ T-cell subsets 11 12.…”

Section: Introductionmentioning

confidence: 99%

Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients

Zhang

Cheng

et al. 2022

Gut

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ObjectiveA comprehensive immune landscape for HBV infection is pivotal to achieve HBV cure.DesignWe performed single-cell RNA sequencing of 2 43 000 cells from 46 paired liver and blood samples of 23 individuals, including six immune tolerant, 5 immune active (IA), 3 acute recovery (AR), 3 chronic resolved and 6 HBV-free healthy controls (HCs). Flow cytometry and histological assays were applied in a second HBV cohort for validation.ResultsBoth IA and AR were characterised by high levels of intrahepatic exhausted CD8+ T (Tex) cells. In IA, Tex cells were mainly derived from liver-resident GZMK+ effector memory T cells and self-expansion. By contrast, peripheral CX3CR1+ effector T cells and GZMK+ effector memory T cells were the main source of Tex cells in AR. In IA but not AR, significant cell–cell interactions were observed between Tex cells and regulatory CD4+ T cells, as well as between Tex and FCGR3A+ macrophages. Such interactions were potentially mediated through human leukocyte antigen class I molecules together with their receptors CANX and LILRBs, respectively, contributing to the dysfunction of antiviral immune responses. By contrast, CX3CR1+GNLY+ central memory CD8+ T cells were concurrently expanded in both liver and blood of AR, providing a potential surrogate marker for viral resolution. In clinic, intrahepatic Tex cells were positively correlated with serum alanine aminotransferase levels and histological grading scores.ConclusionOur study dissects the coordinated immune responses for different HBV infection phases and provides a rich resource for fully understanding immunopathogenesis and developing effective therapeutic strategies.

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Section: Introductionmentioning

confidence: 99%

Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients

Zhang

Cheng

et al. 2022

Gut

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“…In particular, there is an enrichment of TRM cells in HBV patients who enriched viral control in comparison with healthy cases also in presence of the same total T cell frequencies in the liver. Of note, in several cases, virus-specific CD8+ TRM cells can be found in spontaneously recovered HBV patients, thus highlighting the key role of this cell population in the long-term viral control [112][113][114][115].…”

Section: Role Of Hbv Hcv Infection In the Pathogenesis Of Hcc (Early Stages)mentioning

confidence: 95%

Role of Virus-Related Chronic Inflammation and Mechanisms of Cancer Immune-Suppression in Pathogenesis and Progression of Hepatocellular Carcinoma

Borgia

Toffoli

2021

Cancers

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Hepatocellular carcinoma (HCC) can be classified as a prototypical inflammation-driven cancer that generally arises from a background of liver cirrhosis, but that in the presence of nonalcoholic steatohepatitis (NASH), could develop in the absence of fibrosis or cirrhosis. Tumor-promoting inflammation characterizes HCC pathogenesis, with an epidemiology of the chronic liver disease frequently encompassing hepatitis virus B (HBV) or C (HCV). HCC tumor onset and progression is a serial and heterogeneous process in which intrinsic factors, such as genetic mutations and chromosomal instability, are closely associated with an immunosuppressive tumor microenvironment (TME), which may have features associated with the etiopathogenesis and expression of the viral antigens, which favor the evasion of tumor neoantigens to immune surveillance. With the introduction of direct-acting antiviral (DAA) therapies for HCV infection, sustained virological response (SVR) has become very high, although occurrence of HCC and reactivation of HBV in patients with co-infection, who achieved SVR in short term, have been observed in a significant proportion of treated cases. In this review, we discuss the main molecular and TME features that are responsible for HCC pathogenesis and progression. Peculiar functional aspects that could be related to the presence and treatment of HCV/HBV viral infections are also dealt with.

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“…Analysis of circulating immune cells does not necessarily reflect those resident in the liver. 74 Techniques such as second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy imaging are showing great promise in characterizing architectural features of fibrosis at the individual collagen fiber level. 75 Detailed spatial profiling of lymphocyte subsets within parenchymal liver disease is now possible using multiplex immunostaining and digital analysis, massively enriching the depth of information available from the biopsy.…”

Section: Current and Future Roles Of Liver Histologymentioning

confidence: 99%

The Need for Alternatives to Liver Biopsies: Non-Invasive Analytics and Diagnostics

Neuberger

Cain

2021

HMER

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Histology remains essential for the diagnosis and management of many disorders affecting the liver. However, the biopsy procedure itself is associated with a low risk of harm to the patient and cost to the health services; samples may not be adequate and are subject to sampling variation. Furthermore, interpretation often depends on the skill of the pathologist. Increasingly, new techniques are becoming available that are altering the indications for liver biopsy. Many diseases of the liver can be diagnosed and managed using serological and radiological techniques; the degree of fibrosis and fat can often be assessed by serological or imaging techniques and the nature of space occupying lesions defined by serology, imaging and use of liquid biopsy. However, these techniques, too, are subject to limitations: sensitivity and specificity is not always adequate for diagnosis or management; some techniques are expensive and often also require expert interpretation. Although there may be less need for liver biopsy today, histology remains the gold standard as well as an essential tool for the diagnosis and management of many conditions, especially where there are multiple pathologies, or where a diagnosis cannot or has not been made by alternative approaches. Until less invasive techniques become more reliable and accessible, liver histology will remain a key investigation.

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Tissue-Resident Memory T Cells in the Liver—Unique Characteristics of Local Specialists

Cited by 20 publications

References 110 publications

Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients

Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients

Role of Virus-Related Chronic Inflammation and Mechanisms of Cancer Immune-Suppression in Pathogenesis and Progression of Hepatocellular Carcinoma

The Need for Alternatives to Liver Biopsies: Non-Invasive Analytics and Diagnostics

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