Perforin Acts as an Immune Regulator to Prevent the Progression of NAFLD

Wang, Qian; Li, Dehai; Zhu, Jing; Zhang, Mingyue; Zhang, Hua; Cao, Guangchao; Zhu, Leqing; Shi, Qiankun; Hao, Jianlei; Wen, Qiong; Liu, Zonghua; Yang, Hengwen; Yin, Zhinan

doi:10.3389/fimmu.2020.00846

Cited by 3 publications

(1 citation statement)

References 46 publications

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“…A previous microarray study suggested that SERPINE1 and MMP9 might be involved in TGF-β-dependent fibrosis [ 39 ]. An analysis of PRF1-deficient mice demonstrated that PRF1 suppresses high-fat diet-induced NAFLD [ 40 ]. Fas, a member of the TNF receptor superfamily, contributes to mitochondrial dysfunction and the development of steatosis in response to a high-fat diet [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

Roles of Macrophages in Advanced Liver Fibrosis, Identified Using a Newly Established Mouse Model of Diet-Induced Non-Alcoholic Steatohepatitis

Tada

Kasai

Makiuchi

et al. 2022

IJMS

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Macrophages play critical roles in the pathogenesis of non-alcoholic steatohepatitis (NASH). However, it is unclear which macrophage subsets are critically involved in the development of inflammation and fibrosis in NASH. In TSNO mice fed a high-fat/cholesterol/cholate-based diet, which exhibit advanced liver fibrosis that mimics human NASH, we found that Kupffer cells (KCs) were less abundant and recruited macrophages were more abundant, forming hepatic crown-like structures (hCLS) in the liver. The recruited macrophages comprised two subsets: CD11c+/Ly6C− and CD11c−/Ly6C+ cells. CD11c+ cells were present in a mesh-like pattern around the lipid droplets, constituting the hCLS. In addition, CD11c+ cells colocalized with collagen fibers, suggesting that this subset of recruited macrophages might promote advanced liver fibrosis. In contrast, Ly6C+ cells were present in doughnut-like inflammatory lesions, with a lipid droplet in the center. Finally, RNA sequence analysis indicates that CD11c+/Ly6C− cells promote liver fibrosis and hepatic stellate cell (HSC) activation, whereas CD11c−/Ly6C+ cells are a macrophage subset that play an anti-inflammatory role and promote tissue repair in NASH. Taken together, our data revealed changes in liver macrophage subsets during the development of NASH and shed light on the roles of the recruited macrophages in the pathogenesis of advanced fibrosis in NASH.

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Section: Resultsmentioning

confidence: 99%

Roles of Macrophages in Advanced Liver Fibrosis, Identified Using a Newly Established Mouse Model of Diet-Induced Non-Alcoholic Steatohepatitis

Tada

Kasai

Makiuchi

et al. 2022

IJMS

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Non-alcoholic fatty liver disease and intestinal immune status: a narrative review

Lei

Mao

2022

Scandinavian Journal of Gastroenterology

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1

Абатуров¹,

Никулина²

2021

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The literature review presents modern ideas about the role of αβ T cells, which are represented by the main groups: CD4+, CD8+ T lymphocytes and double-negative CD4–CD8– T and double-positive CD4+CD8+ T cells of the adaptive immune system of the organism in the development of metainflammation of adipose tissue in obesity. According to the modern concept, obesity is associated with adipocyte hypertrophy, impaired adipogenesis, the development of metainflammation of adipose tissue that in the early adaptive phase is characterized by the rapid reactivation of memory T cells. The physical connection of cells performing the function of energy storage with immunological memory cells is a special mechanism for the body’s survival during periods of nutritional deficiency. Excess adipose tissue and the appearance of pro-inflammatory hypertrophied adipocytes change the spectrum and ratio of produced adipokines and cytokines, which leads to the recruitment and activation of pro-inflammatory immunocytes and depletion of the pool of anti-inflammatory cells of the innate and adaptive immune system in adipose tissue. Changes in the representation of resident recruited immune cells in adipose tissue during obesity is characterized by the accumulation of pro-inflammatory cells (neutrophils, M1 Mϕ, mast cells, NK, Th1, Th17, Th22 cells) and depletion of regulatory and anti-inflammatory populations (eosinophils, M2 Mϕ, ILC2, iNKT, γδ T, Th2, Treg, B1 cells). Excessive production of interferon γ and tumor necrosis factor α leads to the development of insulin resistance, and interleukin 17 — to degradation of the extracellular matrix of adipose tissue and impaired adipogenesis. In obesity, CD8+ T cells and M1 Mϕ macrophages eliminate hypertrophied adipocytes. A decrease in the activity of Treg cells increases the pro-inflammatory potential of adipose tissue. Despite the progress achieved in disclosing the role of the adaptive immune system in the development of obesity, the antigens associated with adipose tissue, the mechanisms of their generation have not been identified so far, the role of most tissue-specific alarmins has not been determined; the mechanisms that determine the timing, sequence and activity of recruitment of various types of immunocytes are not known. The data of modern studies on the immunopathogenesis of metainflammation of adipose tissue and the creation of drugs that will improve the efficiency and individualize anti-inflammatory therapy in obese patients are presented.

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Perforin Acts as an Immune Regulator to Prevent the Progression of NAFLD

Cited by 3 publications

References 46 publications

Roles of Macrophages in Advanced Liver Fibrosis, Identified Using a Newly Established Mouse Model of Diet-Induced Non-Alcoholic Steatohepatitis

Roles of Macrophages in Advanced Liver Fibrosis, Identified Using a Newly Established Mouse Model of Diet-Induced Non-Alcoholic Steatohepatitis

Non-alcoholic fatty liver disease and intestinal immune status: a narrative review

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