Dataset Information

IFN-γ facilitates liver fibrogenesis by CD161⁺CD4⁺ T cells through a regenerative IL-23/IL-17 axis in chronic hepatitis B virus infection.

ABSTRACT:

Objectives

This study aimed to determine the role of CD161⁺CD4⁺ T cells in chronic hepatitis B virus (HBV) infection.

Methods

A total of 94 patients with chronic hepatitis B (CHB), 73 with liver cirrhosis (LC) and 28 healthy controls were enrolled to determine frequency, cytokine production and chemokine receptor expression of circulating CD161⁺CD4⁺ T cells. Among these, 50 CHB and 34 LC patients were followed up for a period of 52-week entecavir monotherapy to assess the association of CD161⁺CD4⁺ T cells with seroconversion of HBV e antigen (HBeAg). In addition, 15 patients with hepatocellular carcinoma (HCC) and 15 with hepatic haemangioma (HHA) were enrolled to compare the paired circulating and intrahepatic CD161⁺CD4⁺ T cells.

Results

CD161⁺CD4⁺ T cells were found to accumulate in the circulation of HBV cohorts, which showed a significant correlation with the clinical parameters of disease progression. In addition, higher numbers of circulating CD161⁺CD4⁺ T cells were associated with an improved serological response of HBeAg to antiviral treatment. Moreover, CD161⁺CD4⁺ T cells as compared to homologous CD161^-CD4⁺ T cells produced more pro-inflammatory cytokines including interleukin (IL)-17 and interferon (IFN)-γ and expressed higher levels of liver-homing chemokine receptors including CCR6, CXCR6 and CX3CR1. Notably, a significant enrichment of CD161⁺CD4⁺ T cell subsets co-expressing IFN-γ and IL-17 was observed in HBV-associated cirrhotic livers. During in vitro co-cultures, circulating CD161⁺CD4⁺ T cells in the chronic HBV setting exhibited prominent pro-fibrogenic effects by regulating primary hepatic stellate cells through a regenerative IFN-γ/IL-23/IL-17 axis.

Conclusions

In chronic HBV infection, CD161⁺CD4⁺ T cells play antiviral, pro-inflammatory and pro-fibrogenic roles.

SUBMITTER: Li J

PROVIDER: S-EPMC8563156 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IFN-γ facilitates liver fibrogenesis by CD161<sup>+</sup>CD4<sup>+</sup> T cells through a regenerative IL-23/IL-17 axis in chronic hepatitis B virus infection.

Li Jing J Cheng Lisha L Jia Haoyu H Liu Chun C Wang Siqi S Liu Yun Y Shen Yue Y Wu Shengdi S Meng Fanli F Zheng Beishi B Yang Changqing C Jiang Wei W

Clinical & translational immunology 20211102 11

<h4>Objectives</h4>This study aimed to determine the role of CD161<sup>+</sup>CD4<sup>+</sup> T cells in chronic hepatitis B virus (HBV) infection.<h4>Methods</h4>A total of 94 patients with chronic hepatitis B (CHB), 73 with liver cirrhosis (LC) and 28 healthy controls were enrolled to determine frequency, cytokine production and chemokine receptor expression of circulating CD161<sup>+</sup>CD4<sup>+</sup> T cells. Among these, 50 CHB and 34 LC patients were followed up for a period of 52-week ...[more]

PMID: 34754450

Similar Datasets

Project description:In Plasmodium falciparum holoendemic transmission regions of western Kenya, life-threatening pediatric malaria manifests primarily as severe malarial anemia (SMA, Hb≤6.0 g/dL with any density parasitemia). To determine the role that CD4+ T-cell-driven inflammatory responses have in the pathogenesis of SMA, peripheral CD4+ T-cell populations and their intracellular production of pro-inflammatory cytokines (IFN-γ and IL-17) were characterized in children aged 12-36 months of age stratified into two groups: non-severe malarial anemia (non-SMA, Hb≥6.0 g/dL, n = 50) and SMA (n = 39). In addition, circulating IFN-γ and IL-17 were measured as part of a Cytokine 25-plex Antibody Bead Kit, Human (BioSource™ International). Children with SMA had higher overall proportions of circulating lymphocytes (P = 0.003) and elevated proportions of lymphocytes expressing IFN-γ (P = 0.014) and comparable IL-17 (P = 0.101). In addition, SMA was characterized by decreased memory-like T-cells (CD4+CD45RA-) expressing IL-17 (P = 0.009) and lower mean fluorescence intensity in memory-like CD4+ T-cells for both IFN-γ (P = 0.063) and IL-17 (P = 0.006). Circulating concentrations of IFN-γ were higher in children with SMA (P = 0.009), while IL-17 levels were comparable between the groups (P = 0.164). Furthermore, circulating levels of IFN-γ were negatively correlated with IL-17 levels in both groups of children (SMA: r = -0.610, P = 0.007; and non-SMA: r = -0.516, P = 0.001), while production of both cytokines by lymphocytes were positively correlated (SMA: r = 0.349, P = 0.037; and non-SMA: r = 0.475, P = 0.001). In addition, this correlation was only maintained by the memory-like CD4+ T cells (r = 0.365, P = 0.002) but not the naïve-like CD4+ T cells. However, circulating levels of IFN-γ were only associated with naïve-like CD4+ T cells producing IFN-γ (r = 0.547, P = 0.028), while circulating levels of IL-17 were not associated with any of the cell populations. Taken together, these results suggest that enhanced severity of malarial anemia is associated with higher overall levels of circulating lymphocytes, enhanced intracellular production of IFN-γ by peripheral lymphocytes and high circulating IFN-γ levels. In addition, the observed inverse relationship between the circulating levels of IFN-γ and IL-17 together with the reduction in the levels of memory-like CD4+ T cells expressing IL-17 in children with SMA may suggest possible relocation of these cells in the deeper tissues for their pathological effect.

Dataset Information

IFN-γ facilitates liver fibrogenesis by CD161⁺CD4⁺ T cells through a regenerative IL-23/IL-17 axis in chronic hepatitis B virus infection.

Objectives

Methods

Results

Conclusions

Publications

IFN-γ facilitates liver fibrogenesis by CD161<sup>+</sup>CD4<sup>+</sup> T cells through a regenerative IL-23/IL-17 axis in chronic hepatitis B virus infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

IFN-γ facilitates liver fibrogenesis by CD161+CD4+ T cells through a regenerative IL-23/IL-17 axis in chronic hepatitis B virus infection.

Objectives

Methods

Results

Conclusions

Publications

IFN-γ facilitates liver fibrogenesis by CD161<sup>+</sup>CD4<sup>+</sup> T cells through a regenerative IL-23/IL-17 axis in chronic hepatitis B virus infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

IFN-γ facilitates liver fibrogenesis by CD161⁺CD4⁺ T cells through a regenerative IL-23/IL-17 axis in chronic hepatitis B virus infection.