Mesenteric lymph node CD4+ T lymphocytes migrate to liver and contribute to non-alcoholic fatty liver disease

Su, Lin; Wu, Zhe; Chi, Yujing; Song, Yang; Xu, Jianming; Tan, Junjun; Xu, Cong; Liu, Yulan

doi:10.1016/j.cellimm.2019.01.005

Cited by 28 publications

(30 citation statements)

References 42 publications

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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: Discussionmentioning

confidence: 99%

Adaptive immunity: an emerging player in the progression of NAFLD

Sutti

Albano

2019

Nat Rev Gastroenterol Hepatol

264

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: Discussionmentioning

confidence: 99%

Adaptive immunity: an emerging player in the progression of NAFLD

Sutti

Albano

2019

Nat Rev Gastroenterol Hepatol

264

245

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“…As obesity progresses, the number of Treg cells is decreased, concurrently with increased Th17/Treg balance. Animal research has shown that VAT of lean mice is highly enriched with Treg cells, which are markedly reduced in number under obese or insulin-resistant conditions ( 38 , 46 , 96 , 97 ). Several studies conducted on obese and/or T2DM patients also support the above-mentioned phenomenon ( 79 , 87 , 98 – 100 ).…”

Section: The Imbalance Of the Th17/treg Cell Ratio In Visceral Chronic Inflammation And Adipogenesismentioning

confidence: 99%

The Alterations in and the Role of the Th17/Treg Balance in Metabolic Diseases

et al. 2021

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Chronic inflammation plays an important role in the development of metabolic diseases. These include obesity, type 2 diabetes mellitus, and metabolic dysfunction-associated fatty liver disease. The proinflammatory environment maintained by the innate immunity, including macrophages and related cytokines, can be influenced by adaptive immunity. The function of T helper 17 (Th17) and regulatory T (Treg) cells in this process has attracted attention. The Th17/Treg balance is regulated by inflammatory cytokines and various metabolic factors, including those associated with cellular energy metabolism. The possible underlying mechanisms include metabolism-related signaling pathways and epigenetic regulation. Several studies conducted on human and animal models have shown marked differences in and the important roles of Th17/Treg in chronic inflammation associated with obesity and metabolic diseases. Moreover, Th17/Treg seems to be a bridge linking the gut microbiota to host metabolic disorders. In this review, we have provided an overview of the alterations in and the functions of the Th17/Treg balance in metabolic diseases and its role in regulating immune response-related glucose and lipid metabolism.

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“…MLN has been associated with initiation of immunological responses to bacterial translocation and inflammatory bowel diseases (IBDs) [9]. Moreover, it was reported that MLN CD4 + T lymphocytes could migrate to liver and contribute to nonalcoholic fatty liver disease [10]. Our previous study have found that S. japonicum infection could stimulate the responses of multiple immune cells, including Th cells, NK cells, NKT cells, and γδT cells in the B6 mouse MLN [11,12].…”

Section: Introductionmentioning

confidence: 99%

TLR7 Modulated T Cell Response in the Mesenteric Lymph Node of Schistosoma japonicum-Infected C57BL/6 Mice

Jin

et al. 2019

Journal of Immunology Research

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Toll-like receptors (TLRs) play an important role in regulating immune responses during pathogen infection. However, roles of TLRs on T cells reside in the mesenteric lymph node (MLN) were not be fully elucidated in the course of S. japonicum infection. In this study, T lymphocytes from the mesenteric lymph node (MLN) of S. japonicum-infected mice were isolated and the expression and roles of TLR2, TLR3, TLR4, and TLR7 on both CD4+ and CD8+ T cells were compared. We found that the expression of TLR7 was increased in the MLN cells of S. japonicum-infected mice, particularly in CD4+ and CD8+ T cells (P<0.05). R848, a TLR7 agonist, could enhance the production of IFN-γ from MLN T cells of infected mice (P<0.05), especially in CD8+ T cells (P<0.01). In TLR7 gene knockedout (KO) mice, the S. japonicum infection caused a significant decrease (P<0.05) of the expression of CD25 and CD69, as well as the production of IFN-γ and IL-4 inducted by PMA plus ionomycin on both CD4+ and CD8+ T cells. Furthermore, the decreased level of IFN-γ and IL-4 in the supernatants of SEA- or SWA-stimulated mesenteric lymphocytes was detected (P<0.05). Our results indicated that S. japonicum infection could induce the TLR7 expression on T cells in the MLN of C57BL/6 mice, and TLR7 mediates T cell response in the early phase of infection.

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Mesenteric lymph node CD4+ T lymphocytes migrate to liver and contribute to non-alcoholic fatty liver disease

Cited by 28 publications

References 42 publications

Adaptive immunity: an emerging player in the progression of NAFLD

Adaptive immunity: an emerging player in the progression of NAFLD

The Alterations in and the Role of the Th17/Treg Balance in Metabolic Diseases

TLR7 Modulated T Cell Response in the Mesenteric Lymph Node of Schistosoma japonicum-Infected C57BL/6 Mice

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