Mucosal-associated invariant T cells in hepatitis B virus-related liver failure

Xue, Hong; Li, Han; Ju, Linling; Han, Xudong; Cheng, Tiao-Chun; Luo, Xi; Chen, Lin; Shao, Jianghua; She, Yong-jun; Bian, Zhaolian

doi:10.3748/wjg.v26.i31.4703

Cited by 13 publications

(19 citation statements)

References 36 publications

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“…IL-12 plays a key role in enhancing Tfh cell differentiation in our current study, consistent with others ( 10 ). Our findings showed substantially elevated (~2-fold) IL-12 in the serum from HBV-ACLF patients compared to the other three groups, which is consistent with other study ( 26 ). IL-12 is mainly secreted by macrophages, and IL-12 secretion by macrophages is a seminal event in the initiation of the interferon-gamma (IFNγ) immune-activating cytokine cascade.…”

Section: Discussionsupporting

confidence: 93%

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

Teng

Yin

et al. 2021

Front. Immunol.

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ObjectivesT Follicular helper (Tfh) cells, recognized as a distinct CD4+ T cell subset, mediate the development of long-lived humoral immunity via B cell activation/differentiation. Tfh cells play an important role during hepatic viral infection, but its role in hepatitis B virus-related acute on chronic liver failure (HBV-ACLF) remains to be explored.Materials and MethodsThe frequency of Tfh cells, serum pro-inflammatory cytokine (IL-12, IL-21, IL-17 and TNF) levels and IgG/M levels were investigated in HBV-ACLF (n = 36), serious chronic hepatitis B (n = 21), moderate chronic hepatitis B patients (n = 32) and healthy control (HC) subjects (n = 10).ResultsCirculating Tfh cells were significantly increased in HBV-ACLF patients compared to other groups, correlating well with MELD score. However, the frequency of Tfh cells decreased in ameliorated HBV-ACLF patients. Furthermore, serum IL-12 and IL-21 levels were higher in HBV-ACLF patients, compared to other groups. Naïve CD4+ T cells from HC subjects differentiate into Tfh cells following treatment with HBV-ACLF patients’ serum, a process that can be blocked by IL-12/21 neutralizing antibodies. Tfh cells induced by HBV-ACLF patient’s serum promoted the proliferation and IgG production of B cells in vitro. Moreover, circulating CD19+ B cells, serum and liver IgG/M levels were significantly higher in HBV-ACLF patients, compared to other groups.ConclusionsOur data demonstrated that there was a high frequency of Tfh cells and high levels of serum IL-12/21 in HBV-ACLF patients. Naïve CD4+ T cells differentiate into Tfh cells in the presence of HBV-ACLF patients’ serum rich in IL-12/21, which can be blocked by neutralizing IL-12/21 antibodies. These data may provide useful insights for both clinical and basic research in the treatment of HBV-ACLF.

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Section: Discussionsupporting

confidence: 93%

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

Teng

Yin

et al. 2021

Front. Immunol.

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“…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%

“…IL-12 promoted central memory CD8 + T cell response and functionally rescued the exhausted viral-specific CD8 + T cells in chronic HBV infection [ 61 , 62 ]. Xue et al showed that IL-12 levels significantly increased in patients with HBV-related liver failure compared with healthy controls [ 58 ]. In addition, IL-12 can be used as a new marker to assess the degree of inflammation in the development of HCC [ 55 ].…”

Section: Interleukin-12mentioning

confidence: 99%

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

Zhang

Gou

et al. 2022

Mediators of Inflammation

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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.

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“…Our previous study illustrated a significant decline in circulating MAIT cells in patients with HBV-related LF, and we showed that the reduction in MAIT cell levels may be due to stimulation by interleukin (IL)-12 and IL-18. [16] However, alterations in MAIT cells in nonHBV-infected liver failure patients are not clear, nor are the alterations in MAIT cells due to other causes. In this study, we investigated MAIT cell alterations in all LF patients regardless of the cause, and we also focused on the long-term predictive value of the MAIT cell ratio in the prognosis in patients with LF.…”

Section: Introductionmentioning

confidence: 99%

“…Our previous research found that circulating MAIT cells were significantly decreased in HBV-related liver failure patients compared to healthy volunteers. [16]…”

Section: Introductionmentioning

confidence: 99%

MAIT cells predict long-term prognosis in liver failure patients

Cheng

Xue

et al. 2022

Medicine

Self Cite

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Background: Liver failure (LF) is a life-threatening clinical syndrome characterized by intense systemic inflammation and organ failure(s), leading to a high mortality rate. The pathogenesis of LF is multifactorial, immune response, and gut bacterial translocation are thought to be major contributing factors. Mucosal-associated invariant T (MAIT) cells play a critical role in immune response and gut bacterial translocation. We aimed to investigate changes of the MAIT cell ratio in patients with LF and to explore the predictive value for long-term prognosis in patients with LF. Material and Method: We recruited 75 patients with LF from Nantong Third People’s Hospital, isolated peripheral blood mononuclear cells, and detected the proportion of circulating MAIT cells by flow cytometry. Statistical analyses were performed using the GraphPad Prism software. Results: Our data showed that the proportion of MAIT cells alterations was independent of the cause of viral infection in patients with LF. Kaplan-Meier survival analysis showed that LF patients with low level of MAIT cells had poor long-term prognosis. The area under the receiver operating characteristic curve of the MAIT cell proportion was larger than that of the Model for End-Stage Liver Disease (MELD) score. More importantly, the combination of MAIT cell proportion and MELD score had a better effect in predicting long-term prognosis of LF patients than any single index (AUC = 0.91, 95% CI:0.84–0.97), and multivariate logistic regression analysis indicated that the circulating MAIT cell proportion was an independent risk factor for LF. Conclusion: The proportion of MAIT cells in PBMC is an outstanding predictor for the long-term prognosis in patients with LF.

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Mucosal-associated invariant T cells in hepatitis B virus-related liver failure

Cited by 13 publications

References 36 publications

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

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

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

MAIT cells predict long-term prognosis in liver failure patients

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