Increased Circulating T Follicular Helper Cells Induced via IL-12/21 in Patients With Acute on Chronic Hepatitis B Liver Failure

Du, Bingying; Teng, Jiaming; Yin, Rongkun; Tian, Yuanyuan; Jiang, Tingwang; Du, Yanan; Cai, Wei

doi:10.3389/fimmu.2021.641362

Cited by 21 publications

(18 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the course of natural HBV infection, similar to other proinflammatory cytokines, IL-21 elevates significantly at hepatic flare in AHB, CHB, and HBV-ACLF, especially in those achieving resolve or HBsAg seroconversion subsequently (Chen et al, 2014;Yoshio et al, 2018;Du et al, 2021). IL-21 has a pivotal implication in the instruction of antiviral treatment.…”

Section: Interleukin-21mentioning

confidence: 98%

Cytokines and Chemokines in HBV Infection

Zhong

Zhang

Tang

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Chronic hepatitis B virus (HBV) infection remains a leading cause of hepatic inflammation and damage. The pathogenesis of chronic hepatitis B (CHB) infection is predominantly mediated by persistent intrahepatic immunopathology. With the characterization of unique anatomical and immunological structure, the liver is also deemed an immunological organ, which gives rise to massive cytokines and chemokines under pathogenesis conditions, having significant implications for the progression of HBV infection. The intrahepatic innate immune system is responsible for the formidable source of cytokines and chemokines, with the latter also derived from hepatic parenchymal cells. In addition, systemic cytokines and chemokines are disturbed along with the disease course. Since HBV is a stealth virus, persistent exposure to HBV-related antigens confers to immune exhaustion, whereby regulatory cells are recruited by intrahepatic chemokines and cytokines, including interleukin-10 and transforming growth factor β, are involved in such series of causal events. Although the considerable value of two types of available approved treatment, interferons and nucleos(t)ide analogues, effectively suppress HBV replication, neither of them is sufficient for optimal restoration of the immunological attrition state to win the battle of the functional or virological cure of CHB infection. Notably, cytokines and chemokines play a crucial role in regulating the immune response. They exert effects by directly acting on HBV or indirectly manipulating target immune cells. As such, specific cytokines and chemokines, with a potential possibility to serve as novel immunological interventions, combined with those that target the virus itself, seem to be promising prospects in curative CHB infection. Here, we systematically review the recent literature that elucidates cytokine and chemokine-mediated pathogenesis and immune exhaustion of HBV infection and their dynamics triggered by current mainstream anti-HBV therapy. The predictive value of disease progression or control and the immunotherapies target of specific major cytokines and chemokines in CHB infection will also be delineated.

show abstract

Section: Interleukin-21mentioning

confidence: 98%

Cytokines and Chemokines in HBV Infection

Zhong

Zhang

Tang

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…Among CD4 + Th cell subsets, naive CD4 + T cells differentiated into Tfh cells can promote humoral immunity by mediating the interaction between T cells and B cells, which are essential for the control of viral infections and vaccine responses (19)(20)(21). Tfh cells, as a novel CD4 + T cell subset, are characterized by the high expression of CXC chemokine receptor 5 (CXCR5), inducible T cell costimulator (ICOS), programmed cell death protein 1 (PD-1), B-cell lymphoma 6 (Bcl-6), and interleukin-21 (IL-21) in both mice and humans and can usually initiate B cells to differentiate into plasma cells that produce high-affinity antibodies to neutralize the virus, such as lymphocytic choriomeningitis virus (LCMV), influenza virus and hepatitis B virus (22)(23)(24)(25). Loss of Tfh cell function can result in primary immunodeficiencies characterized by impaired humoral immunity, including COVID-19 infection, autosomal-dominant hyper IgE caused by STAT3 deficiency and common variable immunodeficiency (21,25,26).…”

Section: Introductionmentioning

confidence: 99%

Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection

et al. 2021

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious infectious disease that has led to a global pandemic with high morbidity and mortality. High-affinity neutralizing antibody is important for controlling infection, which is closely regulated by follicular helper T (Tfh) cells. Tfh cells play a central role in promoting germinal center reactions and driving cognate B cell differentiation for antibody secretion. Available studies indicate a close relationship between virus-specific Tfh cell-mediated immunity and SARS-CoV-2 infection progression. Although several lines of evidence have suggested that Tfh cells contribute to the control of SARS-CoV-2 infection by eliciting neutralizing antibody productions, further studies are needed to elucidate Tfh-mediated effector mechanisms in anti-SARS-CoV-2 immunity. Here, we summarize the functional features and roles of virus-specific Tfh cells in the immunopathogenesis of SARS-CoV-2 infection and in COVID-19 vaccines, and highlight the potential of targeting Tfh cells as therapeutic strategy against SARS-CoV-2 infection.

show abstract

“…IL-12 is secreted primarily by macrophages, which are key to initiating the cascade of immune-activated cytokines IFN- γ . Clinical studies have found that serum IL-12 in patients with HBV-ACLF is significantly elevated (approximately 2 times) compared with severe chronic hepatitis B, moderate chronic hepatitis B, and healthy controls [ 57 , 58 ]. IL-12 induces IL-21 through transcription factors STAT1, STAT3, STAT4, and STAT5 [ 59 ] and enhances T follicular helper (Tfh) cells differentiation [ 60 ].…”

Section: Interleukin-12mentioning

confidence: 99%

“…Upregulation of Tfh cells and IL-21 show a close association with the severity/improvement of HBV-ACLF. Serum of patients with HBV-ACLF rich in IL-21 enhances the differentiation of primary CD4 + T cells into Tfh cells, and this interaction can be blocked by anti-IL-21 antibodies [ 57 ]. The production of IL-21 was significantly correlated with the number of Tfh cells, clinical score, and liver function (ALT/AST), verifying the important role of IL-21 in Tfh cell generation during the occurrence of HBV-ACLF [ 57 ].…”

Section: Interleukin-21mentioning

confidence: 99%

“…Serum of patients with HBV-ACLF rich in IL-21 enhances the differentiation of primary CD4 + T cells into Tfh cells, and this interaction can be blocked by anti-IL-21 antibodies [ 57 ]. The production of IL-21 was significantly correlated with the number of Tfh cells, clinical score, and liver function (ALT/AST), verifying the important role of IL-21 in Tfh cell generation during the occurrence of HBV-ACLF [ 57 ]. However, other studies have shown that there is no obvious correlation between the frequency of CD4 + IL-21 T cells and MELD score or survival rate of HBV-ACLF patients [ 91 ].…”

Section: Interleukin-21mentioning

confidence: 99%

See 1 more Smart Citation

Serum Interleukins as Potential Prognostic Biomarkers in HBV-Related Acute-on-Chronic Liver Failure

Zhang

Gou

et al. 2022

Mediators of Inflammation

View full text Add to dashboard Cite

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is relatively common in China and has complex pathogenesis, difficult clinical treatment, and poor prognosis. Immune status is an important factor affecting ACLF prognosis. Interleukins are a family of secreted lymphocyte factors that interact with a host of cell types including immune cells. These signaling molecules play important roles in transmitting information; regulating immune cells; mediating the activation, proliferation, and differentiation of T and B cells; and modulating inflammatory responses. Many studies have investigated the correlation between interleukin expression and the prognosis of HBV-ACLF. This review focuses on the potential use of interleukins as prognostic biomarkers in HBV-ACLF. References were mainly identified through PubMed and CNKI search, including relevant studies published until December 2021. We have summarized reports of several promising diagnostic interleukin biomarkers that predict susceptibility to HBV-ACLF. The use of biomarkers to understand early prognosis can help devise different therapeutic measures and improve patient survival. Ongoing research on prognostic biomarkers of HBV-ACLF is promising, and future preclinical and clinical studies are warranted.

show abstract

Increased Circulating T Follicular Helper Cells Induced via IL-12/21 in Patients With Acute on Chronic Hepatitis B Liver Failure

Cited by 21 publications

References 34 publications

Cytokines and Chemokines in HBV Infection

Cytokines and Chemokines in HBV Infection

Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection

Serum Interleukins as Potential Prognostic Biomarkers in HBV-Related Acute-on-Chronic Liver Failure

Contact Info

Product

Resources

About