Mesenteric adipose tissue B lymphocytes promote local and hepatic inflammation in non‐alcoholic fatty liver disease mice

Wu, Zhe; Xu, Jianming; Tan, Junjun; Song, Yang; Liu, Ling; Zhang, Feng; Zhang, Yifan; Li, Xia; Chi, Yujing; Liu, Yulan

doi:10.1111/jcmm.14232

Cited by 25 publications

(39 citation statements)

References 37 publications

(82 reference statements)

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“…Nonetheless, several unresolved issues remain in understanding the mechanisms by which adaptive immunity can contribute to NAFLD evolution (box 1). For instance, evidence suggesting that B cells and CD4 + T cells infiltrating the liver in NASH originate from mesenteric lymph nodes and inflamed mesenteric adipose tissue 126,127 raises the question of how gut-liver interactions influence NASH-associated adaptive immunity. In this setting, an additional question concerns the mechanism by which NAFLD affects the liver tolerogenic milieu to favour OSE presentation by APCs to B cells and T cells.…”

Section: Resultsmentioning

confidence: 99%

Adaptive immunity: an emerging player in the progression of NAFLD

Sutti

Albano

2019

Nat Rev Gastroenterol Hepatol

263

245

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In the past decade, nonalcoholic fatty liver disease (NAFLD) has become a leading cause of chronic liver disease and cirrhosis, as well as an important risk factor for hepatocellular carcinoma (HCC). NAFLD encompasses a spectrum of liver lesions, including simple steatosis, steatohepatitis and fibrosis. Although steatosis is often harmless, the lobular inflammation that characterizes nonalcoholic steatohepatitis (NASH) is considered a driving force in the progression of NAFLD. The current view is that innate immune mechanisms represent a key element in supporting hepatic inflammation in NASH. However, increasing evidence points to the role of adaptive immunity as an additional factor promoting liver inflammation. This Review discusses data regarding the role of B cells and T cells in sustaining the progression of NASH to fibrosis and HCC, along with the findings that antigens originating from oxidative stress act as a trigger for immune responses. We also highlight the mechanisms affecting liver immune tolerance in the setting of steatohepatitis that favour lymphocyte activation. Finally , we analyse emerging evidence concerning the possible application of immune modulating treatments in NASH therapy.

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Section: Resultsmentioning

confidence: 99%

Adaptive immunity: an emerging player in the progression of NAFLD

Sutti

Albano

2019

Nat Rev Gastroenterol Hepatol

263

245

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“…B-1 and B-2 cells coexist in perivascular AT, epicardial WAT and BAT, where the B1:B2 ratio is higher than that in sub-cutaneous WAT but yet varies greatly in a depot-specific manner (321,322). B cells are among the first immune cells to infiltrate AT following the consumption of a HFD consistent with an increased IR, where AT B-2 cells are thought to promote inflammation (323)(324)(325)(326)(327). B cell abundance also increases in BAT following the consumption of a HFD, where their role is poorly understood (328).…”

Section: B Cellsmentioning

confidence: 99%

“…MAT is located between the gut and the liver. Several lines of evidence associate MAT expansion to an elevated risk for the development of peripheral and central IR as well as CVDs (327,420). In response to HFD consumption, MAT adipocytes secrete high amounts of MCP-1, which intensifies the inflammatory response by modulating macrophage infiltration driving IR and atherosclerosis (421).…”

Section: Mesenteric Adipose Tissuementioning

confidence: 99%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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Adipose tissue is a critical regulator of systemic metabolism and bodily homeostasis as it secretes a myriad of adipokines, including inflammatory and anti-inflammatory cytokines. As the main storage pool of lipids, subcutaneous and visceral adipose tissues undergo marked hypertrophy and hyperplasia in response to nutritional excess leading to hypoxia, adipokine dysregulation, and subsequent low-grade inflammation that is characterized by increased infiltration and activation of innate and adaptive immune cells. The specific localization, physiology, susceptibility to inflammation and the heterogeneity of the inflammatory cell population of each adipose depot are unique and thus dictate the possible complications of adipose tissue chronic inflammation. Several lines of evidence link visceral and particularly perivascular, pericardial, and perirenal adipose tissue inflammation to the development of metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular diseases. In addition to the implication of the immune system in the regulation of adipose tissue function, adipose tissue immune components are pivotal in detrimental or otherwise favorable adipose tissue remodeling and thermogenesis. Adipose tissue resident and infiltrating immune cells undergo metabolic and morphological adaptation based on the systemic energy status and thus a better comprehension of the metabolic regulation of immune cells in adipose tissues is pivotal to address complications of chronic adipose tissue inflammation. In this review, we discuss the role of adipose innate and adaptive immune cells across various physiological and pathophysiological states that pertain to the development or progression of cardiovascular diseases associated with metabolic disorders. Understanding such mechanisms allows for the exploitation of the adipose tissue-immune system crosstalk, exploring how the adipose immune system might be targeted as a strategy to treat cardiovascular derangements associated with metabolic dysfunctions.

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“…This is also shown by a generalized moderate upregulation of pro-inflammatory signaling cascades in overweight and obesity. Important mediators in this context include interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNFα) [ 10 , 11 , 12 ]. Moreover, a downregulation of anti-inflammatory mediators such as IL-10 has been reported [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Important mediators in this context include interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNFα) [ 10 , 11 , 12 ]. Moreover, a downregulation of anti-inflammatory mediators such as IL-10 has been reported [ 12 ]. All of the above mentioned mediators take part in well-orchestrated and tightly regulated signaling cascades and derailments of them may be responsible for a LGI-mediated interaction between obesity and NAFLD [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Dietary-Induced Low-Grade Inflammation in the Liver

et al. 2020

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The literature describes a close correlation between metabolic disorders and abnormal immune responses, like low-grade inflammation (LGI), which may be one mechanistic link between obesity and various comorbidities, including non-alcoholic fatty liver disease (NAFLD). In our study, we investigated the influence of dietary composition on obesity-derived LGI in the liver. We used a dietary induced obesity mouse model of C57BL/6J mice fed with high fat diet (HFD, 60% fat, 20% protein, 20% carbohydrates) and two different controls. One was rich in carbohydrates (10% fat, 20% protein, 70% carbohydrates), further referred to as the control diet (CD), and the other one is referred to as the standard diet (SD), with a more balanced macronutrient content (9% fat, 33% protein, 58% carbohydrates). Our results showed a significant increased NAFLD activity score in HFD compared to both controls, but livers of the CD group also differed in their macroscopic appearance from healthy livers. Hepatic fat content showed significantly elevated cholesterol concentrations in the CD group. Histologic analysis of the cellular immune response in the liver showed no difference between HFD and CD and expression analysis of immunologic mediators like interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor alpha also point towards a pro-inflammatory response to CD, comparable to LGI in HFD. Therefore, when studying diet-induced obesity with a focus on inflammatory processes, we encourage researchers to carefully select controls and not use a control diet disproportionally rich in carbohydrates.

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Mesenteric adipose tissue B lymphocytes promote local and hepatic inflammation in non‐alcoholic fatty liver disease mice

Cited by 25 publications

References 37 publications

Adaptive immunity: an emerging player in the progression of NAFLD

Adaptive immunity: an emerging player in the progression of NAFLD

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Dietary-Induced Low-Grade Inflammation in the Liver

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