Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease

Dou, Liping; Chen, Yi-fa; Thomson, Angus W.; Chen, Xiaoping

doi:10.1055/s-0038-1646949

Cited by 49 publications

(38 citation statements)

References 112 publications

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“…Additionally, cDC depletion in DTR mice in acetaminophen (APAP) hepatotoxicity could exacerbate liver injury in a manner independent of neutrophils, natural killer (NK) cells or inflammatory mediators 7 . For other liver disorders, the dysfunction of DCs has also been described in previous studies 8 . However, the characterization of cDCs during AIH and the underlying mechanism remain to be elucidated.…”

Section: Introductionsupporting

confidence: 59%

Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation

et al. 2020

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Autoimmune hepatitis (AIH) is a necroinflammatory disease associated with interactive cell populations of the innate and adaptive immune systems. The contribution of conventional dendritic cells (cDCs) to AIH and the underlying mechanism remain poorly understood. The frequency of peripheral mature cDCs increased in AIH patients and was positively correlated with disease severity. In experimental autoimmune hepatitis (EAH), hepatic accumulation of mature cDCs was observed, along with an increase in the periphery. Sequentially, bone marrow-derived dendritic cells (BMDC) from EAH mice exhibit more proinflammatory function than those from control mice. In vitro, ConA treatment promotes the maturation of BMDCs, which are characterized by higher expression of MHC-II, costimulatory molecules and cytokine secretion. ConA also induced the expression of autophagy-related protein and the formation of autophagosomes in DCs. To further investigate whether ConA-induced DC activation is associated with autophagy, we utilized 3-MA and bafilomycin A1 to block autophagy flux and accessed the maturation and function of DCs induced by ConA. 3-MA and bafilomycin A1 inhibited the mature status and proinflammatory cytokine secretion and diminished the proliferation and differentiation of CD4+ T cells when ConA-induced BMDCs cocultured CD4+ T cells. We demonstrated that cDCs contribute to the pathogenesis of AIH through excessive maturation. Aberrant autophagy flux plays a vital role in the immunogenic maturation of cDCs in AIH, and tolerogenic cDCs by inhibition of autophagy flux can be exploited as a new therapeutic approach for AIH.

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Section: Introductionsupporting

confidence: 59%

Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation

et al. 2020

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“…Hepatic dendritic cells show an immature phenotype, with a lower expression of MHC and costimulatory molecules (i.e., CD40, CD86, and CD80), poor endocytotic capacity and low IL-12 production, compared to their peripheral counterparts (81,82). As reported for HDCs, low level expression of costimulatory and MHC class I and II molecules at the steady state makes also KCs, LSECs, and HSCs poorly efficient in , such as TGF-β and IL-10 can be produced by expanded regulatory T cells (Treg) as well as by stellate cells (HSCs), dendritic cells (DCs) and Kupffer cells (KCs).…”

Section: Tolerogenic Apcmentioning

confidence: 99%

Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches

et al. 2020

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“…Several reports claim that the impairment of MDC function and production of cytokines (IL-12, TNF-α, IFN-α/IFN-β) in chronic HCV infection. [344][345][346] Laursen et al examined soluble CD163 released from activated liver macrophages in chronic HCV, and histological activity after DAAs. They found that serum CD163 levels decline rapidly after successful DAAs therapy and are associated with histological inflammatory activity and fibrosis.…”

Section: Daas Treatment On Innate Immunitymentioning

confidence: 99%

<p>Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment</p>

Dash¹,

Aydın²,

Widmer³

et al. 2020

JHC

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Hepatitis C virus (HCV) infection is the major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of HCC initiation, growth, and metastasis appear to be highly complex due to the decade-long interactions between the virus, immune system, and overlapping bystander effects of host metabolic liver disease. The lack of a readily accessible animal model system for HCV is a significant obstacle to understand the mechanisms of viral carcinogenesis. Traditionally, the primary prevention strategy of HCC has been to eliminate infection by antiviral therapy. The success of virus elimination by antiviral treatment is determined by the SVR when the HCV is no longer detectable in serum. Interferon-alpha (IFNα) and its analogs, pegylated IFN-α (PEG-IFN-α) alone with ribavirin (RBV), have been the primary antiviral treatment of HCV for many years with a low cure rate. The cloning and sequencing of HCV have allowed the development of cell culture models, which accelerated antiviral drug discovery. It resulted in the selection of highly effective direct-acting antiviral (DAA)-based combination therapy that now offers incredible success in curing HCV infection in more than 95% of all patients, including those with cirrhosis. However, several emerging recent publications claim that patients who have liver cirrhosis at the time of DAAs treatment face the risk of HCC occurrence and recurrence after viral cure. This remains a substantial challenge while addressing the long-term benefit of antiviral medicine. The host-related mechanisms that drive the risk of HCC in the absence of the virus are unknown. This review describes the multifaceted mechanisms that create a tumorigenic environment during chronic HCV infection. In addition to the potential oncogenic programming that drives HCC after viral clearance by DAAs, the current status of a biomarker development for early prediction of cirrhosis regression and HCC detection post viral treatment is discussed. Since DAAs treatment does not provide full protection against reinfection or viral transmission to other individuals, the recent studies for a vaccine development are also reviewed.

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Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease

Cited by 49 publications

References 112 publications

Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation

Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation

Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches

<p>Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment</p>

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