Bile acid restrained T cell activation explains cholestasis aggravated hepatitis B virus infection

Ding, Chujie; Yu, Hong; Che, Yuan; He, Tianyu; Wang, Yun; Zhang, Shule; Wu, Jiawei; Xu, Wanfeng; Hou, Jingyi; Hao, Haiping; Cao, Lijuan

doi:10.1096/fj.202200332r

Cited by 14 publications

(9 citation statements)

References 48 publications

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“…In addition, the host amino acid metabolism was significantly changed during African swine fever virus infection [ 19 ]. Bile acid plays a key role in resisting hepatitis B virus infection via controlling the activation and metabolism of T cells [ 20 ]. Therefore, it is an important antiviral strategy to explore the mechanism of various virus regulating the metabolism of host cells.…”

Section: Discussionmentioning

confidence: 99%

Integrated Metabolomic and transcriptomic analyses reveal deoxycholic acid promotes transmissible gastroenteritis virus infection by inhibiting phosphorylation of NF-κB and STAT3

Zhou,

Xu,

et al. 2024

BMC Genomics

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Background Acute diarrhea, dehydration and death in piglets are all symptoms of transmissible gastroenteritis virus (TGEV), which results in significant financial losses in the pig industry. It is important to understand the pathogenesis and identify new antiviral targets by revealing the metabolic interactions between TGEV and host cells. Results We performed metabolomic and transcriptomic analyses of swine testicular cells infected with TGEV. A total of 1339 differential metabolites and 206 differentially expressed genes were detected post TEGV infection. The differentially expressed genes were significantly enriched in the HIF-1 signaling pathway and PI3K-Akt signaling. Integrated analysis of differentially expressed genes and differential metabolites indicated that they were significantly enriched in the metabolic processes such as nucleotide metabolism, biosynthesis of cofactors and purine metabolism. In addition, the results showed that most of the detected metabolites involved in the bile secretion was downregulated during TGEV infection. Furthermore, exogenous addition of key metabolite deoxycholic acid (DCA) significantly enhanced TGEV replication by NF-κB and STAT3 signal pathways. Conclusions We identified a significant metabolite, DCA, related to TGEV replication. It added TGEV replication in host cells by inhibiting phosphorylation of NF-κB and STAT3. This study provided novel insights into the metabolomic and transcriptomic alterations related to TGEV infection and revealed potential molecular and metabolic targets for the regulation of TGEV infection.

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Section: Discussionmentioning

confidence: 99%

Integrated Metabolomic and transcriptomic analyses reveal deoxycholic acid promotes transmissible gastroenteritis virus infection by inhibiting phosphorylation of NF-κB and STAT3

Zhou,

Xu,

et al. 2024

BMC Genomics

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“…Previous studies described dysfunctional T cell response in cholestatic mice. Mechanistically, this might be attributed to bile acids disrupting intracellular calcium homeostasis, which is essential for T cell activation and results in poor hepatitis outcome (Ding et al, 2022). In addition, an increasing Frontiers in Pharmacology frontiersin.org number of monocyte-derived macrophages were activated and recruited to cholestatic liver, which was attributed to inflammasome activation and proinflammatory cytokine secretion brought on by hydrophobic bile acids stimulation (Duwaerts et al, 2013;Gong et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Uncovering key molecules and immune landscape in cholestatic liver injury: implications for pathogenesis and drug therapy

Song

Geng

et al. 2023

Front. Pharmacol.

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Background: Cholestasis is a common pathological process in a variety of liver diseases that may lead to liver fibrosis, cirrhosis, and even liver failure. Cholestasis relief has been regarded as a principal target in the management of multiple chronic cholestasis liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) at present. However, complicated pathogenesis and limited acknowledgments fettered therapeutic development. Therefore, this study aimed to systematically analyze miRNA-mRNA regulatory networks in cholestatic liver injury in order to provide new treatment strategies.Methods: Gene Expression Omnibus (GEO) database (GSE159676) was used to screen differentially expressed hepatic miRNAs and mRNAs in the PSC vs. control comparison and the PBC vs. control comparison, respectively. MiRWalk 2.0 tool was used to predict miRNA-mRNA pairs. Subsequently, functional analysis and immune cell infiltration analysis were performed to explore the pivotal functions of the target genes. RT-PCR was used to verify the result.Results: In total, a miRNA-mRNA network including 6 miRNAs (miR-122, miR-30e, let-7c, miR-107, miR-503, and miR-192) and 8 hub genes (PTPRC, TYROBP, LCP2, RAC2, SYK, TLR2, CD53, and LAPTM5) was constructed in cholestasis. Functional analysis revealed that these genes were mainly involved in the regulation of the immune system. Further analysis revealed that resting memory CD4 T cells and monocytes could potentially participate in cholestatic liver injury. The expressions of DEMis and eight hub genes were verified in ANIT-induced and BDL-induced cholestatic mouse models. Furthermore, SYK was found to have an impact on the response to UDCA, and its mechanism was possibly associated with complement activation and monocyte reduction.Conclusion: In the present study, a miRNA-mRNA regulatory network was constructed in cholestatic liver injury, which mostly mediated immune-related pathways. Moreover, the targeted gene SYK and monocytes were found to be related to UDCA response in PBC.

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“…BA metabolites also disrupt intracellular calcium homeostasis, which is critical for the nuclear factor for activating T cells (NFAT) signaling and T cell activation [ 160 ]. 24-Nourrsodeoxycholic acid (NorUDCA) alters the immunometabolism of CD8 + T cells and attenuates hepatic inflammation [ 161 ].…”

Section: Immunological Mechanisms Of Gut Microbiota In the Pathogenes...mentioning

confidence: 99%

The Role of Gut Microbiota in Neuromyelitis Optica Spectrum Disorder

Yao,

Yang,

Cen

et al. 2024

IJMS

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Neuromyelitis optica spectrum disorder (NMOSD) is a rare, disabling inflammatory disease of the central nervous system (CNS). Aquaporin-4 (AQP4)-specific T cells play a key role in the pathogenesis of NMOSD. In addition to immune factors, T cells recognizing the AQP4 epitope showed cross-reactivity with homologous peptide sequences in C. perfringens proteins, suggesting that the gut microbiota plays an integral role in the pathogenicity of NMOSD. In this review, we summarize research on the involvement of the gut microbiota in the pathophysiology of NMOSD and its possible pathogenic mechanisms. Among them, Clostridium perfringens and Streptococcus have been confirmed to play a role by multiple studies. Based on this evidence, metabolites produced by gut microbes, such as short-chain fatty acids (SCFAs), tryptophan (Trp), and bile acid (BA) metabolites, have also been found to affect immune cell metabolism. Therefore, the role of the gut microbiota in the pathophysiology of NMOSD is very important. Alterations in the composition of the gut microbiota can lead to pathological changes and alter the formation of microbiota-derived components and metabolites. It can serve as a biomarker for disease onset and progression and as a potential disease-modifying therapy.

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Bile acid restrained T cell activation explains cholestasis aggravated hepatitis B virus infection

Cited by 14 publications

References 48 publications

Integrated Metabolomic and transcriptomic analyses reveal deoxycholic acid promotes transmissible gastroenteritis virus infection by inhibiting phosphorylation of NF-κB and STAT3

Integrated Metabolomic and transcriptomic analyses reveal deoxycholic acid promotes transmissible gastroenteritis virus infection by inhibiting phosphorylation of NF-κB and STAT3

Uncovering key molecules and immune landscape in cholestatic liver injury: implications for pathogenesis and drug therapy

The Role of Gut Microbiota in Neuromyelitis Optica Spectrum Disorder

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