Interferon-induced IL-10 drives systemic T-cell dysfunction during chronic liver injury

Hackstein, Carl-Philipp; Spitzer, Jasper; Symeonidis, Konstantinos; Horvatic, Helena; Bedke, Tanja; Steglich, Babett; Klein, Sabine; Assmus, Lisa Mareike; Odainic, Alexandru; Szlapa, Jennifer; Kessler, Nina; Beyer, Marc; Schmithausen, Ricarda Maria; Latz, Eicke; Flavell, Richard A.; Garbi, Natalio; Kurts, Christian; Kümmerer, Beate M.; Trebicka, Jonel; Roers, Axel; Huber, Samuel; Schmidt, Susanne V.; Knolle, Percy A.; Abdullah, Zeinab

doi:10.1016/j.jhep.2023.02.026

Cited by 7 publications

(4 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data, which mainly show a cellular immune response, are consistent with the reduction of the rate of severe disease and mortality in individuals with cirrhosis vaccinated against COVID-19 compared to unvaccinated patients rather than a lower infection rate [124]. On the other hand, a recent trial analyzing T cells from cirrhotic patients following COVID-19 vaccination showed that CD4+ and CD8+ T cells produce significantly lower levels of IFN gamma when exposed in vitro to spike protein peptides [120]. Furthermore, a specific subset of T cells, known as mucosal-associated invariant T cells (MAITs), which possess a semi-invariant TCR that recognizes riboflavin from microorganisms presented by antigen-presenting cells through the MHC-I-related protein 1 (MR1), appears to be involved in the COVID-19 vaccination response.…”

Section: Cirrhosis Immune Dysfunction and Defective Immunizationsupporting

confidence: 71%

See 1 more Smart Citation

Vaccine Responses in Patients with Liver Cirrhosis: From the Immune System to the Gut Microbiota

Airola,

Andaloro,

Gasbarrini

et al. 2024

Vaccines

View full text Add to dashboard Cite

Vaccines prevent a significant number of deaths annually. However, certain populations do not respond adequately to vaccination due to impaired immune systems. Cirrhosis, a condition marked by a profound disruption of immunity, impairs the normal immunization process. Critical vaccines for cirrhotic patients, such as the hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcal, and coronavirus disease 19 (COVID-19), often elicit suboptimal responses in these individuals. The humoral response, essential for immunization, is less effective in cirrhosis due to a decline in B memory cells and an increase in plasma blasts, which interfere with the creation of a long-lasting response to antigen vaccination. Additionally, some T cell subtypes exhibit reduced activation in cirrhosis. Nonetheless, the persistence of memory T cell activity, while not preventing infections, may help to attenuate the severity of diseases in these patients. Alongside that, the impairment of innate immunity, particularly in dendritic cells (DCs), prevents the normal priming of adaptive immunity, interrupting the immunization process at its onset. Furthermore, cirrhosis disrupts the gut–liver axis balance, causing dysbiosis, reduced production of short-chain fatty acids (SCFAs), increased intestinal permeability, and bacterial translocation. Undermining the physiological activity of the immune system, these alterations could impact the vaccine response. Enhancing the understanding of the molecular and cellular factors contributing to impaired vaccination responses in cirrhotic patients is crucial for improving vaccine efficacy in this population and developing better prevention strategies.

show abstract

Section: Cirrhosis Immune Dysfunction and Defective Immunizationsupporting

confidence: 71%

“…Molecular and transcriptomic studies showed an increase in the expression of genes related to T cell-exhausted phenotypes, such as Tox, Batf, Irf4, and Id3 [120]. CD8+ T cells in cirrhotic patients overexpress surface immune checkpoint molecules like PD-1, CTLA-4, and TIM-3 [121,122].…”

Section: Cirrhosis Immune Dysfunction and Defective Immunizationmentioning

confidence: 99%

Vaccine Responses in Patients with Liver Cirrhosis: From the Immune System to the Gut Microbiota

Airola,

Andaloro,

Gasbarrini

et al. 2024

Vaccines

View full text Add to dashboard Cite

show abstract

“…as a crucial mediator of T-cell dysfunction during chronic HBV infection and HIV-1/HCV coinfection diseases [52,53]. Altogether, these observations highlight the important role of the 14-pb Ins/Del and + 3142 C > G polymorphisms of HLA-G 3'UTR in the susceptibility to various infectious diseases including the HBV infection.…”

Section: Declarationsmentioning

confidence: 99%

Association of HLA-G 3’UTR Polymorphisms with hepatitis B virus infection in Tunisian population

Laaribi,

Mehri,

Yahia

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Hepatitis B virus (HBV) infection is a major public health burden. The mechanisms of immune evasion during chronic HBV (CHB) infection are poorly understood. Human leukocyte antigen (HLA)-G, an immune checkpoint molecule, plays a crucial role in the tolerance mechanisms of various infectious diseases. The 3’untranslated region (3’UTR), including the HLA-G + 3142C > G polymorphism (rs1063320) and the 14-pb Ins/Del (rs66554220) has been strongly suggested to influence HLA-G expression. Objective This study conducted a case-control analysis to evaluate the potential correlation between the HLA-G + 3142 C > G polymorphism and HBV infection outcome in a Tunisian cohort. Methods The HLA-G + 3142C > G polymorphism was analysed by PCR-RFLP in 242 patients with chronic HBV infection, 241 healthy controls, and 100 spontaneously resolved subjects. Results Patients with chronic HBV infection showed a higher frequency of the + 3142 G allele compared to healthy controls and spontaneously resolved subjects (p = 0.001 and p = 0.002, respectively). An association between the + 3142 G allele and high HBV DNA levels was observed when HBV patients were stratified based on their HBV DNA levels (p = 0.016). Furthermore, the dominant model (GG + GC vs CC) was associated with liver function parameters, including AST, ALT, and high HBV DNA levels (p = 0.04, p < 0.001 and p = 0.002, respectively). However, there was no significant association found between this polymorphism and the fibrosis stage (p = 0.32). The haplotype analysis, using a subset of previously published data on the HLA-G 14pb Ins/Del polymorphism, revealed an association between the Ins/G haplotype and chronic HBV infection (H1: InsG, p < 0.001). Conclusion Our findings suggest that the + 3142 G allele is a risk factor for the persistence and progression of HBV infection, while the + 3142 C allele serves as a protective allele associated with the spontaneous resolution of the infection. Additionally, the HLA-G 3’UTR haplotype Ins/G is associated with chronic HBV infection in the Tunisian population.

show abstract

“…ILCs can produce different subsets of cytokines depending on their lineage and polarization, such as IFN-γ, IL-4, IL-5, IL-9, IL-13, IL-17, and IL-22 that can regulate inflammation, tissue repair and mucosal immunity. γδ T cells can produce IFN-γ, TNF-α, IL-17 and IL-22 that can modulate inflammation, antimicrobial defense, and epithelial barrier function 49 . Opportunistic gut pathogens are microorganisms capable of inducing disease in individuals with compromised immune systems.…”

Section: Innate Lymphocytes May Recognize Increased Opportunistic Gut...mentioning

confidence: 99%

A comprehensive perspective on the interaction between gut microbiota and COVID-19 vaccines

Hong

Lan

et al. 2023

Gut Microbes

View full text Add to dashboard Cite

The efficacy of COVID-19 vaccines varies between individuals and populations, and the reasons for this are still not fully understood. Recent clinical studies and animal models have indicated that the gut microbiota may influence the immunogenicity of the vaccine and, thus, its effectiveness. This suggests that there is a bidirectional relationship between the gut microbiota and the COVID-19 vaccine, with the varying components of the microbiota either enhancing or reducing the vaccine’s efficacy. To put an end to the spread of the COVID-19 pandemic, the necessity of vaccines that create powerful and long-term immunity is now more important than ever, and understanding the role of the gut microbiota in this process is essential. Conversely, COVID-19 vaccines also have a significant effect on the gut microbiota, decreasing its total number of organisms and the variety of species present. In this Review, we analyze the evidence that suggesting an interaction between the gut microbiota and COVID-19 vaccine effectiveness, consider the immunological mechanisms that may be responsible for this connection, and explore the possibility of using gut microbiota-focused interventions to improve the efficacy of COVID-19 vaccines.

show abstract

Interferon-induced IL-10 drives systemic T-cell dysfunction during chronic liver injury

Cited by 7 publications

References 38 publications

Vaccine Responses in Patients with Liver Cirrhosis: From the Immune System to the Gut Microbiota

Vaccine Responses in Patients with Liver Cirrhosis: From the Immune System to the Gut Microbiota

Association of HLA-G 3’UTR Polymorphisms with hepatitis B virus infection in Tunisian population

A comprehensive perspective on the interaction between gut microbiota and COVID-19 vaccines

Contact Info

Product

Resources

About