Crosstalk Between Liver Macrophages and Surrounding Cells in Nonalcoholic Steatohepatitis

Li, Haiou; Zhou, Yunjiao; Wang, Haizhou; Zhang, Meng; Qiu, Peishan; Zhang, Mengna; Zhang, Ruike; Zhao, Qiu; Liu, Jing

doi:10.3389/fimmu.2020.01169

Cited by 76 publications

(64 citation statements)

References 108 publications

(135 reference statements)

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“…The frequencies of different immune cell compartments are altered during NAFLD and the specific role of some of these immune cell populations in promoting NASH has been well-established. For example, KCs are enriched in NASH livers, where produce inflammatory cytokines and facilitate the development of fibrosis and HCC [reviewed in ( 12 , 13 )]. Likewise, neutrophils, are recruited into the liver during NASH in response to several chemokines contributing to the progression of NASH and pathogenesis of HCC ( 14 ).…”

Section: Inflammation As the Hallmark Of The Progression From Non-alcmentioning

confidence: 99%

Revisiting the Role of Natural Killer Cells in Non-Alcoholic Fatty Liver Disease

2021

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Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common form of chronic liver disease. The histological spectrum of NAFLD ranges from simple steatosis to chronic inflammation and liver fibrosis during Non-Alcoholic Steatohepatitis (NASH). The current view is that innate immune mechanisms represent a key element in supporting hepatic inflammation in NASH. Natural Killer (NK) cells are lymphoid cells and a component of the innate immune system known to be involved in NASH progression. Increasing evidence has shed light on the differential function of circulating and tissue-resident NK cells, as well as on the relevance of metabolism and the microenvironment in regulating their activity. Here, we revisit the complex role of NK cells as regulators of NASH progression as well as potential therapeutic approaches based on their modulation.

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Section: Inflammation As the Hallmark Of The Progression From Non-alcmentioning

confidence: 99%

Revisiting the Role of Natural Killer Cells in Non-Alcoholic Fatty Liver Disease

2021

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“…While hepatic expression of CSF1 has been previously shown to be upregulated in NASH 14 , to our knowledge, no prior study has linked a decline in CSF1 with an improvement in NAFLD severity. Nonetheless, given that Kupffer cells are key players in NAFLD initiation and progression 23 , 24 , it is plausible that a strategy that blunts the activity of this cell population would attenuate the course of disease. Notably, while CSF1 receptor antagonists have been studied with great interest in the context of various inflammatory disorders 19 , their use in chronic liver disease has yet to be explored.…”

Section: Discussionmentioning

confidence: 99%

Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach

Fourman

Stanley

Billingsley

et al. 2021

Sci Rep

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NAFLD is a leading comorbidity in HIV with an exaggerated course compared to the general population. Tesamorelin has been demonstrated to reduce liver fat and prevent fibrosis progression in HIV-associated NAFLD. We further showed that tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. Nonetheless, effects of tesamorelin on individual plasma proteins pertaining to these pathways are not known. Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets. Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log2-fold change − 0.20 ± 0.35 vs. 0.05 ± 0.34, P = 0.02), transforming growth factor beta 1 (TGFB1, − 0.35 ± 0.56 vs. − 0.05 ± 0.43, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, − 0.17 ± 0.21 vs. 0.02 ± 0.20, P = 0.004) versus placebo. Among tesamorelin-treated participants, reductions in plasma VEGFA (r = 0.62, P = 0.006) and CSF1 (r = 0.50, P = 0.04) correlated with a decline in NAFLD activity score. Decreases in TGFB1 (r = 0.61, P = 0.009) and CSF1 (r = 0.64, P = 0.006) were associated with reduced gene-level fibrosis score. Tesamorelin suppressed key angiogenic, fibrogenic, and pro-inflammatory mediators. CSF1, a regulator of monocyte recruitment and activation, may serve as an innovative therapeutic target for NAFLD in HIV. Clinical Trials Registry Number: NCT02196831

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“…Inflammation is a major driver of pathology in this disease, eventually responsible for the evolution to irreversible fibrosis driven by remodeling of the extracellular matrix under the constant insults propelled by pro-inflammatory signals [ 56 ]. Macrophages and, particularly, the M1 population are at least in part responsible for these alterations [ 57 ]. M1 macrophages produce both pro-inflammatory and immuno-stimulatory cytokines, particularly interleukin (IL)-12, IL-6, IL-1α, TNF-α and IL-1β, and create an environment that is microbicidal in the context of the innate immune response and leads to cell death.…”

Section: Cic and Citrate Are Important Mediators Of Inflammationmentioning

confidence: 99%

The Mitochondrial Citrate Carrier SLC25A1/CIC and the Fundamental Role of Citrate in Cancer, Inflammation and Beyond

et al. 2021

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The mitochondrial citrate/isocitrate carrier, CIC, has been shown to play an important role in a growing list of human diseases. CIC belongs to a large family of nuclear-encoded mitochondrial transporters that serve the fundamental function of allowing the transit of ions and metabolites through the impermeable mitochondrial membrane. Citrate is central to mitochondrial metabolism and respiration and plays fundamental activities in the cytosol, serving as a metabolic substrate, an allosteric enzymatic regulator and, as the source of Acetyl-Coenzyme A, also as an epigenetic modifier. In this review, we highlight the complexity of the mechanisms of action of this transporter, describing its involvement in human diseases and the therapeutic opportunities for targeting its activity in several pathological conditions.

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Crosstalk Between Liver Macrophages and Surrounding Cells in Nonalcoholic Steatohepatitis

Cited by 76 publications

References 108 publications

Revisiting the Role of Natural Killer Cells in Non-Alcoholic Fatty Liver Disease

Revisiting the Role of Natural Killer Cells in Non-Alcoholic Fatty Liver Disease

Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach

The Mitochondrial Citrate Carrier SLC25A1/CIC and the Fundamental Role of Citrate in Cancer, Inflammation and Beyond

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