Expansion of dysfunctional CD56‐CD16+ NK cells in chronic hepatitis B patients

Wijaya, Ratna Sari; Read, Scott A.; Schibeci, Stephen D.; Han, Shuanglin; Azardaryany, Mahmoud Karimi; Poorten, David van der; Lin, Rita; Yuen, Lawrence; Lam, Vincent; Douglas, Mark W.; George, Jacob; Ahlenstiel, Golo

doi:10.1111/liv.14784

Cited by 16 publications

(10 citation statements)

References 79 publications

(193 reference statements)

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“…By contrast, during chronic HBV (CHB) infection, NK cells display fewer activating and more inhibitory receptors and lose effector functions, particularly the capacity to secrete cytokines [ 72 , 73 ]. These findings are consistent with recent studies describing the expansion of dysfunctional CD56 - CD16 + NK cells and a transcriptional NK cell profile similar to that of exhausted T cells in CHB patients [ 74 , 76 ]. NK cell dysfunction in CHB patients is mediated by elevated expression of immunosuppressive cytokines such as IL-10 and TGF-β [ 75 , 76 ].…”

Section: Viral Infections Of the Liversupporting

confidence: 93%

The role of natural killer cells in liver inflammation

et al. 2021

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The liver is an important immunological site that can promote immune tolerance or activation. Natural killer (NK) cells are a major immune subset within the liver, and therefore understanding their role in liver homeostasis and inflammation is crucial. Due to their cytotoxic function, NK cells are important in the immune response against hepatotropic viral infections but are also involved in the inflammatory processes of autoimmune liver diseases and fatty liver disease. Whether NK cells primarily promote pro-inflammatory or tolerogenic responses is not known for many liver diseases. Understanding the involvement of NK cells in liver inflammation will be crucial in effective treatment and future immunotherapeutic targeting of NK cells in these disease settings. Here, we explore the role that NK cells play in inflammation of the liver in the context of viral infection, autoimmunity and fatty liver disease.

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Section: Viral Infections Of the Liversupporting

confidence: 93%

The role of natural killer cells in liver inflammation

et al. 2021

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“…Consistently, in our study, we confirmed the expansion of the CD56 neg NK cell population. Similarly, expansion of CD56 neg NK cells has also been observed during infections with other viruses, including HCV, cytomegalovirus, Epstein-Barr virus, and HBV (36)(37)(38)(39). More recently, unconventional CD56 neg NK cells were shown to result from aberrant maturation of conventional NK cells, and a high frequency of CD56 neg NK cells was found to be associated with adverse clinical outcomes in acute lymphoblastic leukemia (40).…”

Section: Discussionmentioning

confidence: 88%

Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression

et al. 2022

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BackgroundPopulations of natural killer cells lacking CD56 expression [CD56neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their roles during disease progression remain poorly understood.MethodsIn this study, 84 donors, namely 34 treatment-naïve HIV-1-infected patients (TNs), 29 HIV-1-infected patients with successful antiretroviral therapy (ARTs), and 21 healthy controls (HCs), were enrolled. The phenotypic and functional characteristics of CD56neg NK cells were analyzed using single-cell RNA-sequencing (scRNA-seq) and flow cytometry. A potential link between the characteristics of CD56neg NK cells and the clinical parameters associated with HIV-1 disease progression was examined.ResultsThe frequency of the CD56neg NK cell population was significantly increased in TNs, which could be partially rescued by ART. Flow cytometry analyses revealed that CD56neg NK cells were characterized by high expression of CD39, TIGIT, CD95, and Ki67 compared to CD56dim NK cells. In vitro assays revealed reduced IFN-γ and TNF-α secretion, as well as decreased expression of granzyme B and perforin in CD56neg NK cells. In line with the data obtained by flow cytometry, scRNA-seq analysis further demonstrated impaired cytotoxic activities of CD56neg NK cells. Notably, a negative correlation was observed between CD39, CD95, and Ki67 expression levels in CD56neg NK cells and CD4+ T cell counts.ConclusionsThe results presented in this study indicate that the CD56neg NK cell population expanded in HIV-1-infected individuals is dysfunctional and closely correlates with HIV-1 disease progression.

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“…Our results suggested that the frequency of NK cells was reduced under the condition of pregnancy. Studies have reported that NK cells play a major role in the occurrence of CHB ( 7 – 10 ). HBV virus can damage and inhibit the function of NK cells ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of Antiviral Therapy During Pregnancy on Natural Killer Cells in Pregnant Women With Chronic HBV Infection

et al. 2022

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ObjectiveTo study the effect of antiviral therapy during pregnancy on the frequency of natural killer (NK) cells in peripheral blood of women with HBV DNA positive chronic hepatitis B (CHB).MethodIn total 124 female subjects were divided into four groups: 11 healthy non-pregnant women (Normal group), 26 non-pregnant women in immune tolerance period of chronic hepatitis B virus (HBV) infection (CHB group), 41 pregnant CHB women without antiviral treatment during pregnancy (Untreated group), and 46 pregnant CHB women receiving antiviral treatment during pregnancy (Treated group). The frequency of NK cells in peripheral blood were detected by flow cytometry.ResultThe frequency of NK cells in healthy women [15.30 (12.80, 18.40)] was higher than that in women with HBV infection, but there was no significant statistical difference (p=0.436). The frequency of NK cells in CHB group [10.60 (6.00, 18.30)] was higher than those in pregnant CHB women [Untreated: 6.90 (4.89, 10.04), P=0.001; Treated: 9.42 (6.55, 14.10), P=0.047]. The frequency of NK cells in treated group was significantly higher than that in untreated group (P = 0.019). The frequencies of NK cells, CD56bright NK cells and NKp46dim NK cells at 12 and 24 weeks postpartum in the untreated group were increased significantly than those before delivery. In treated group, the frequencies of NK cells, CD56bright NK cells, NKp46+ NK cells and NKp46dim NK cells were significantly increased at 6 and 12 weeks than those before delivery. The frequencies of NK cells and CD56bright NK cells postpartum were increased significantly in treated group than those in untreated group. The frequencies of CD56dim NK cells decreased significantly after delivery in treated than those in untreated patients. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) significantly increased after delivery than those before delivery. The results showed that the postpartum ALT level was weak positive correlated with NKp46high frequency (r=0.199) and was weak negative correlated with NKp46dim frequency (r= -0.199).ConclusionAntiviral treatment during pregnancy could significantly increase the frequency of NK cells postpartum. Postpartum hepatitis may be related to the immune injury caused by change of NK cell frequency and HBV infection.

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Expansion of dysfunctional CD56‐CD16+ NK cells in chronic hepatitis B patients

Cited by 16 publications

References 79 publications

The role of natural killer cells in liver inflammation

The role of natural killer cells in liver inflammation

Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression

Effect of Antiviral Therapy During Pregnancy on Natural Killer Cells in Pregnant Women With Chronic HBV Infection

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