IL-17A in Human Liver: Significant Source of Inflammation and Trigger of Liver Fibrosis Initiation

Kartasheva-Ebertz, Daria; Gaston, Jésintha; Lair-Mehiri, Loriane; Mottez, Estelle; Buivan, Tan-Phuc; Massault, Pierre-Philippe; Scatton, Olivier; Gaujoux, Sébastien; Vaillant, Jean Christophe; Pol, Stanislas; Lagaye, Sylvie

doi:10.3390/ijms23179773

Cited by 11 publications

(5 citation statements)

References 34 publications

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“…Ghazavi et al found the same with a significant difference [26]. Indeed, Th17 cells are the main source of IL-17 production which stimulates the secretion of IL-8, which is a potent chemoattractant of neutrophils involved in conditions such as COVID-19 [27,28].…”

Section: Discussionmentioning

confidence: 89%

Kinetics of Cytokines and Anti-SARS-CoV-2 Spike Glycoprotein S1 IgM and IgG1 in COVID-19 Infected Patients in Togo

2023

Infect Dis Diag Treat

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Background: COVID-19, caused by, had spread throughout the world. Its clinical manifestations ranged from asymptomatic to severe forms. The immunological markers that determine these forms are poorly investigated in Togo. This study aimed to investigate the dynamics of antibodies and cytokines in COVID-19 infected patients in Togo. Methodology: Sera from symptomatic (n = 40) and asymptomatic (n = 40) patients, collected at Day0, Day3 and Day10 post admission, were analyzed for SARS-CoV-2 specific IgM and IgG1 antibodies and IL-1b, IL-6, TNFa, IL-5, IL-10, IL-17A and IFNg by sandwich ELISA. Results: In response to SARS-CoV-2 infection, IgM was expressed first followed by IgG1 in symptomatic patients. However, in asymptomatic patients, these antibodies were expressed simultaneously from the beginning of the infection with higher titers of IgG1. Except of IL-1b that increased from the admission to D10 all other cytokines were elevated at the admission and decreased to D10. Serum IL-6 levels were three times higher in symptomatic compared to asymptomatic patients. Conclusion: COVID-19 asymptomatic patients were characterized by high IgG1 antibodies titers whereas COVID-19 symptomatic patients, by high IL-6 levels.

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Section: Discussionmentioning

confidence: 89%

Kinetics of Cytokines and Anti-SARS-CoV-2 Spike Glycoprotein S1 IgM and IgG1 in COVID-19 Infected Patients in Togo

2023

Infect Dis Diag Treat

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“…Interestingly, correlation analysis of KEGG demonstrated significant enrichment of multiple autoimmune disease-related pathways such as rheumatoid arthritis, asthma, inflammatory bowel disease, and Th17 cell differentiation. Th17 cell differentiation pathway has been closely related to hepatitis, fibrosis, and autoimmune diseases ( Beringer and Miossec, 2018 ; Kartasheva-Ebertz et al., 2022 ). Therefore, these findings explain the “hygiene hypothesis” to some extent, but further in-depth research is necessary ( Bach, 2017 ; Caraballo, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver

Zhan,

Wu,

Deng

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionClonorchiasis remains a serious global public health problem, causing various hepatobiliary diseases. However, there is still a lack of overall understanding regarding the molecular events triggered by Clonorchis sinensis (C. sinensis) in the liver.MethodsBALB/c mouse models infected with C. sinensis for 5, 10, 15, and 20 weeks were constructed. Liver pathology staining and observation were conducted to evaluate histopathology. The levels of biochemical enzymes, blood routine indices, and cytokines in the blood were determined. Furthermore, alterations in the transcriptome, proteome, and metabolome of mouse livers infected for 5 weeks were analyzed using multi-omics techniques.ResultsThe results of this study indicated that adult C. sinensis can cause hepatosplenomegaly and liver damage, with the most severe symptoms observed at 5 weeks post-infection. However, as the infection persisted, the Th2 immune response increased and symptoms were relieved. Multi-omics analysis of liver infected for 5 weeks identified 191, 402 and 232 differentially expressed genes (DEGs), proteins (DEPs) and metabolites (DEMs), respectively. Both DEGs and DEPs were significantly enriched in liver fibrosis-related pathways such as ECM-receptor interaction and cell adhesion molecules. Key molecules associated with liver fibrosis and inflammation (Cd34, Epcam, S100a6, Fhl2, Itgax, and Retnlg) were up-regulated at both the gene and protein levels. The top three metabolic pathways, namely purine metabolism, arachidonic acid metabolism, and ABC transporters, were associated with liver cirrhosis, fibrosis, and cholestasis, respectively. Furthermore, metabolites that can promote liver inflammation and fibrosis, such as LysoPC(P-16:0/0:0), 20-COOH-leukotriene E4, and 14,15-DiHETrE, were significantly up-regulated.ConclusionOur study revealed that the most severe symptoms in mice infected with C. sinensis occurred at 5 weeks post-infection. Moreover, multi-omics analysis uncovered predominant molecular events related to fibrosis changes in the liver. This study not only enhances our understanding of clonorchiasis progression but also provides valuable insights into the molecular-level interaction mechanism between C. sinensis and its host liver.

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“…Th17 and mucosal-associated invariant T (MAIT) cells in the liver secreted IL-17 A, which triggered fibrosis via inducing the expression of IL-6 and other pro-fibrotic markers thus suggesting that IL-17A could be a target for anti-fibrotic treatment ( 41 ). Both IL-17A and Th17 related cytokines including IL-6 and TGF-β1 participated in the progress of liver cirrhosis.…”

Section: Novel Advances Targeting Immune Factorsmentioning

confidence: 99%

Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?

Yang

Rojas

et al. 2023

Front. Immunol.

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Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC is multifactorial and involves immune dysregulation, abnormal bile metabolism, and progressive fibrosis, ultimately leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are currently used as first- and second-line treatments, respectively. However, many patients do not respond adequately to UDCA, and the long-term effects of these drugs are limited. Recent research has advanced our understanding the mechanisms of pathogenesis in PBC and greatly facilitated development of novel drugs to target mechanistic checkpoints. Animal studies and clinical trials of pipeline drugs have yielded promising results in slowing disease progression. Targeting immune mediated pathogenesis and anti-inflammatory therapies are focused on the early stage, while anti-cholestatic and anti-fibrotic therapies are emphasized in the late stage of disease, which is characterized by fibrosis and cirrhosis development. Nonetheless, it is worth noting that currently, there exists a dearth of therapeutic options that can effectively impede the progression of the disease to its terminal stages. Hence, there is an urgent need for further research aimed at investigating the underlying pathophysiology mechanisms with potential therapeutic effects. This review highlights our current knowledge of the underlying immunological and cellular mechanisms of pathogenesis in PBC. Further, we also address current mechanism-based target therapies for PBC and potential therapeutic strategies to improve the efficacy of existing treatments.

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IL-17A in Human Liver: Significant Source of Inflammation and Trigger of Liver Fibrosis Initiation

Cited by 11 publications

References 34 publications

Kinetics of Cytokines and Anti-SARS-CoV-2 Spike Glycoprotein S1 IgM and IgG1 in COVID-19 Infected Patients in Togo

Kinetics of Cytokines and Anti-SARS-CoV-2 Spike Glycoprotein S1 IgM and IgG1 in COVID-19 Infected Patients in Togo

Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver

Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?

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