scholarly journals Dendritic Cells and T Cell Subsets in the Development of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis

2021 ◽  
Vol 48 (3) ◽  
pp. 49-55
Author(s):  
M. Gulubova ◽  
M. Hadzhi ◽  
L. Hadzhiilieva ◽  
D. Chonov ◽  
M. M. Ignatova
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
T Cell Subsets ◽  
Γδt Cells ◽  
Nonalcoholic Fatty Liver ◽  
Th22 Cells

Abstract Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are associated with steatosis, inflammation and fibrosis. Liver dendritic cells (DCs) are usually tolerogenic in the sinusoidal milleu composed of immunosuppressive cytokines. In NAFLD and NASH, DCs become pro-inflammatory and modulate hepatic immune response. Murine liver DCs are three major subtypes: classical (lymphoid) cDC1 or the crosspresenters (CD8α+CD103+), classical (myeloid) cDC2 (CD11b+) and plasmacytoid pDCs (PDCA-1+Siglec-H+) and two additional subtypes or lymphoid + myeloid DCs and NKDCs. Similarly, human liver DCs are three subtypes or CD141+CLEC9A+, CD1c+ (BDCA1+) and pDCs (CD303+BDCA2+). Compared to blood human hepatic DCs are less immature and predominantly induce regulatory T cells (Tregs) and IL-4 secreting T cells (Th2). DCs polarize T cells into different Th types that are in interrelations in NAFLD/NASH. T helper 1 (Th1) (T-bet) cells are associated with adipose tissue inflammation. The differentiation of Th2 (GATA3) cells is induced by IL-4 DCs, increased in NAFLD. Similarly, Th17 cells (RORγt/ RORc) are increased in NAFLD and NASH. Tregs (FoxP3) are increased in the liver in steatosis and Th22 cells (AHR) are elevated in diabetes mellitus 2 (DM2) and adiposity. CD8+ T cells γδT cells and MAIT cells also contribute to liver inflammation.

scholarly journals T Cell Subsets and Natural Killer Cells in the Pathogenesis of Nonalcoholic Fatty Liver Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12190
Author(s):  
Yoseph Asmelash Gebru ◽  
Haripriya Gupta ◽  
Hyeong Seop Kim ◽  
Jung A. Eom ◽  
Goo Hyun Kwon ◽  
...  
Keyword(s):  
T Cells ◽  
Liver Disease ◽  
T Cell ◽  
Fatty Liver ◽  
Nk Cells ◽  
Nonalcoholic Fatty Liver Disease ◽  
Natural Killer ◽  
Fatty Liver Disease ◽  
T Cell Subsets ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by hepatic accumulation of excess lipids. T cells are commonly classified into various subsets based on their surface markers including T cell receptors, type of antigen presentation and pathophysiological functions. Several studies have implicated various T cell subsets and natural killer (NK) cells in the progression of NAFLD. While NK cells are mainly components of the innate hepatic immune system, the majority of T cell subsets can be part of both the adaptive and innate systems. Several studies have reported that various stages of NAFLD are accompanied by the accumulation of distinct T cell subsets and NK cells with different functions and phenotypes observed usually resulting in proinflammatory effects. More importantly, the overall stimulation of the intrahepatic T cell subsets is directly influenced by the homeostasis of the gut microbiota. Similarly, NK cells have been found to accumulate in the liver in response to pathogens and tumors. In this review, we discussed the nature and pathophysiological roles of T cell subsets including γδ T cells, NKT cells, Mucosal-associated invariant T (MAIT) cells as well as NK cells in NAFLD.

scholarly journals Elevated Th22 cells correlated with Th17 cells in patients with high liver stiffness in nonalcoholic fatty liver disease

2018 ◽  
Vol 16 ◽  
pp. 205873921880267 ◽  
Author(s):  
Si-Biao Su ◽  
Wen Chen ◽  
Fei-Fei Huang ◽  
Jian-Feng Zhang
Keyword(s):  
Flow Cytometry ◽  
Liver Disease ◽  
Plasma Level ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Th17 Cells ◽  
Liver Stiffness ◽  
Nonalcoholic Fatty Liver ◽  
Th22 Cells

The aims of this article are to investigate the effects of Th22 and Th17 cells and plasma cytokines in patients with nonalcoholic fatty liver disease (NAFLD) and to examine the correlation between Th22 and Th17 cells levels and disease progression. Blood samples from 70 patients with NAFLD and 26 healthy controls (HCs) were collected. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were performed. ELISA revealed interleukin (IL)-22 plasma level in FibroScan subgroup patients was 2.2-fold higher than that in the HCs ( P < 0.01), body mass index (BMI) subgroup patients were 2.3-fold higher than HCs ( P < 0.01), IL-17A plasma level was 5.6-fold higher in FibroScan subgroup patients than that in the HCs ( P < 0.01), and 5.8-fold higher in BMI subgroup than HCs ( P < 0.01). Flow cytometry revealed median proportions of Th22 cells in FibroScan group was greater than that in the HCs (3.85% vs 0.86%; P < 0.001). Similar results were obtained for Th17 cells (6.36% vs 0.9%; P < 0.001). The liver stiffness measurement value was highly correlated with the proportion of Th17 and Th22 cells and moderately correlated with the plasma level of IL-17A, IL-22, and the BMI value. In conclusion, the elevated proportions of Th17 and Th22 cells were significantly correlated with the degree of liver cirrhosis in NAFLD patients. They may play an inflammatory and immune response role in progression from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) or fibrosis.

scholarly journals Hepatic Immune Microenvironment in Alcoholic and Nonalcoholic Liver Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jin-Seok Byun ◽  
Hyon-Seung Yi
Keyword(s):  
T Cells ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Natural Killer ◽  
Alcoholic Liver Disease ◽  
Immune Cells ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

Many types of innate (natural killer cells, natural killer T cells, and Kupffer cells/macrophages) and adaptive (T cells and B cells) immune cells are enriched within the liver and function in liver physiology and pathology. Liver pathology is generally induced by two types of immunologic insults: failure to eliminate antigens derived from the gastrointestinal tract which are important for host defense and an impaired tissue protective tolerance mechanism that helps reduce the negative outcomes of immunopathology. Accumulating evidence from the last several decades suggests that hepatic immune cells play an important role in the pathogenesis of alcoholic and nonalcoholic liver injury and inflammation in humans and mice. Here, we focus on the roles of innate and adaptive immune cells in the development and maintenance of alcoholic liver disease and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Additionally, the pathogenesis of liver disease and new therapeutic targets for preventing and treating alcoholic liver disease and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis are discussed.

scholarly journals The Role of Dendritic Cells in Fibrosis Progression in Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Paloma Almeda-Valdes ◽  
Nancy E. Aguilar Olivos ◽  
Beatriz Barranco-Fragoso ◽  
Misael Uribe ◽  
Nahum Méndez-Sánchez
Keyword(s):  
Dendritic Cells ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Current Evidence ◽  
Pathophysiological Mechanism ◽  
Main Function ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease. NAFLD encompasses a wide range of pathologies, from simple steatosis to steatosis with inflammation to fibrosis. The pathogenesis of NAFLD progression has not been completely elucidated, and different liver cells could be implicated. This review focuses on the current evidence of the role of liver dendritic cells (DCs) in the progression from NAFLD to fibrosis. Liver DCs are a heterogeneous population of hepatic antigen-presenting cells; their main function is to induce T-cell mediated immunity by antigen processing and presentation to T cells. During the steady state liver DCs are immature and tolerogenic. However, in an environment of chronic inflammation, DCs are transformed to potent inducers of immune responses. There is evidence about the role of DC in liver fibrosis, but it is not clearly understood. Interestingly, there might be a link between lipid metabolism and DC function, suggesting that immunogenic DCs are associated with liver lipid storage, representing a possible pathophysiological mechanism in NAFLD development. A better understanding of the interaction between inflammatory pathways and the different cell types and the effect on the progression of NAFLD is of great relevance.

scholarly journals Immunoregulatory Effect of Koumine on Nonalcoholic Fatty Liver Disease Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Rongcai Yue ◽  
Guilin Jin ◽  
Shanshan Wei ◽  
Huihui Huang ◽  
Li Su ◽  
...  
Keyword(s):  
T Cells ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Treg Cells ◽  
Immunomodulatory Activity ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome

Nonalcoholic fatty liver disease (NAFLD) is the most common and important chronic liver disease all over the world. In the present study, we found that koumine, the main and active ingredient isolated from Gelsemium elegans, has the potential therapeutic effect on NAFLD rats by immunomodulatory activity. Koumine could significantly reduce the level of TG, TC, LDL-C, ALT, and AST in the serum of NAFLD rats and increase the level of HDL-C, reduce the liver index, and improve the adipose-like lesions of liver cells in NAFLD rats. Furthermore, treatment with koumine inhibited the severity of NAFLD. In addition, koumine-treated rats significantly increased the proportion of CD4+/CD8+ T cells and also decreased the percentages of Th1 and Th17 cells and increased Th2 and Treg cells in the liver. Moreover, koumine reduced the production and mRNA expression of proinflammatory cytokines in vivo. This result showed that koumine could effectively modulate different subtypes of helper T cells and prevent NAFLD. The present study revealed the novel immunomodulatory activity of koumine and highlighted the importance to further investigate the effects of koumine on hepatic manifestation of the metabolic syndrome.

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