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CD4+ CD25+ FOXP3+ T regulatory cells (Tregs) are a subset of the immunomodulatory cell population that can inhibit both innate and adaptive immunity by various regulatory mechanisms. In hepatic microenvironment, proliferation, plasticity, migration, and function of Tregs are interrelated to the remaining immune cells and their secreted cytokines and chemokines. In normal conditions, Tregs protect the liver from inflammatory and auto-immune responses, while disruption of this crosstalk between Tregs and other immune cells may result in the progression of chronic liver diseases and the development of hepatic malignancy. In this review, we analyze the deviance of this protective nature of Tregs in response to chronic inflammation and its involvement in inducing liver fibrosis, cirrhosis, and hepatocellular carcinoma. We will also provide a detailed emphasis on the relevance of Tregs as an effective immunotherapeutic option for autoimmune diseases, liver transplantation, and chronic liver diseases including liver cancer., SCOPUS: re.j, info:eu-repo/semantics/published

Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation at both the global and the transcript-specific levels. In this study, we characterized translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) by polysome profiling. We demonstrate that protein synthesis increases during exit from pluripotency and is then globally repressed during later steps of hepatogenic maturation. This global downregulation of translation is accompanied by a decrease in the abundance of protein components of the translation machinery, which involves a global reduction in translational efficiency of terminal oligopyrimidine tract (TOP) mRNA encoding translation-related factors. Despite global translational repression during hepatogenic differentiation, key hepatogenic genes remain efficiently translated, and the translation of several transcripts involved in hepatospecific functions and metabolic maturation is even induced. We conclude that, during hepatogenic differentiation, a global decrease in protein synthesis is accompanied by a specific translational rewiring of hepatospecific transcripts.

Background Kupffer cells (KC) are embryonically derived liver resident macrophages, responsible for maintaining liver homeostasis. Apart from KCs, infiltrating mono-macrophages of bone marrow origin also make up a small proportion of the hepatic macrophage population. During chronic liver diseases, the Kupffer cell population is largely replaced by the infiltrating mono-macrophage populations. Thus, the hepatic macrophage populations differ in their origin, phenotype, and characteristics. So, maintaining a balance between the different hepatic macrophage populations determines the outcome of the progression of chronic liver diseases. Aim To study the miRNA-based epigenetic dysregulation of KCs and infiltrating macrophages during chronic liver diseases. Methods- C57BL/6 mice were intraperitoneally injected with carbon tetrachloride (CCl4) twice a week for 4 and 18 weeks to induce progressive liver damage. Enzymatic digestion of the liver using collagenase was performed to isolate non-parenchymal cell fractions (NPF). Cell sorting using specific surface antibodies was performed to isolate KCs and infiltrating mono-macrophages from the NPF of digested livers. Results The overall leukocyte cell population was found to be slightly increased in the CCl4 groups than oil-treated group. The overall frequency of the myeloid cell population remained the same between the vehicle and CCl4-treated groups. The frequency of KCs is decreased in both CCl4-treated mice liver groups (20%-25% of total myeloid cell population) in comparison to the vehicle-treated group (60% of myeloid cell population), while the frequency of mono-macrophages was found to be initially increased in the 4 weeks CCl4 treated group (25% of myeloid cells) and then decreased in the 18 weeks CCl4 treated group (10% of myeloid cells). Conclusion Our preliminary results suggest a dynamic change in the hepatic macrophage populations during chronic liver disease conditions. During the initial stage of CCl4-induced l

Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation at both the global and the transcript-specific levels. In this study, we characterized translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) by polysome profiling. We demonstrate that protein synthesis increases during exit from pluripotency and is then globally repressed during later steps of hepatogenic maturation. This global downregulation of translation is accompanied by a decrease in the abundance of protein components of the translation machinery, which involves a global reduction in translational efficiency of terminal oligopyrimidine tract (TOP) mRNA encoding translation-related factors. Despite global translational repression during hepatogenic differentiation, key hepatogenic genes remain efficiently translated, and the translation of several transcripts involved in hepatospecific functions and metabolic maturation is even induced. We conclude that, during hepatogenic differentiation, a global decrease in protein synthesis is accompanied by a specific translational rewiring of hepatospecific transcripts., SCOPUS: ar.j, info:eu-repo/semantics/published