scholarly journals CD4+RORγt++ and Tregs in a Mouse Model of Diet-Induced Nonalcoholic Steatohepatitis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Luisa Vonghia ◽  
Nathalie Ruyssers ◽  
Dorien Schrijvers ◽  
Paul Pelckmans ◽  
Peter Michielsen ◽  
...  

Background and Aims. Inflammatory mediators that cross-talk in different metabolically active organs are thought to play a crucial role in the pathogenesis of Nonalcoholic Steatohepatitis (NASH). This study was aimed at investigating the CD4+RORγt+ T-helper cells and their counterpart, the CD4+CD25+FOXP3+ regulatory T cells in the liver, subcutaneous adipose tissue (SAT), and abdominal adipose tissue (AAT) in a high fat diet (HFD) mouse model.Methods. C57BL6 mice were fed a HFD or a normal diet (ND). Liver enzymes, metabolic parameters, and liver histology were assessed. The expression of CD4+RORγt+ cells and regulatory T cells in different organs (blood, liver, AAT, and SAT) were analyzed by flow cytometry. Cytokine and adipokine tissue expression were studied by RT-PCR.Results. Mice fed a HFD developed NASH and metabolic alterations compared to normal diet. CD4+RORγt++ cells were significantly increased in the liver and the AAT while an increase of regulatory T cells was observed in the SAT of mice fed HFD compared to ND. Inflammatory cytokines were also upregulated.Conclusions. CD4+RORγt++ cells and regulatory T cells are altered in NASH with a site-specific pattern and correlate with the severity of the disease. These site-specific differences are associated with increased cytokine expression.

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052098094
Author(s):  
Shuang Qin ◽  
Li Li ◽  
Jia Liu ◽  
Jinrui Zhang ◽  
Qing Xiao ◽  
...  

Objective The present study aimed to evaluate the effects of cluster of differentiation (CD)4+CD25+ forkhead box p3 (Foxp3)+ regulatory T cells (Tregs) on unexplained recurrent spontaneous abortion (URSA) and the associated mechanisms. Methods The proportion of CD4+CD25+Foxp3+ Tregs and inflammatory cytokine concentrations in the peripheral blood of women with URSA were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. CBA/JxDBA/2J mating was used to establish an abortion-prone mouse model and the model mice were treated with the Toll-like receptor 4 (TLR4) antagonist E5564 and the TLR4 agonist lipopolysaccharide. Results The proportion of CD4+CD25+Foxp3+ Tregs was decreased and the inflammatory response was increased in women with URSA. In the abortion-prone mouse model, E5564 significantly increased the proportion of CD4+CD25+Foxp3+ Tregs, decreased the inflammatory response, and increased Foxp3 mRNA and protein expression. Lipopolysaccharide had adverse effects on the abortion-prone model. Conclusions These data suggest that CD4+CD25+Foxp3+ Tregs regulate immune homeostasis in URSA via the TLR4/nuclear factor-κB pathway, and that the TLR4 antagonist E5564 may be a novel and potential drug for treating URSA.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A926-A926
Author(s):  
Heidi Griesmann ◽  
Heidi Griesmann ◽  
Heidi Griesmann ◽  
Christof Drexel ◽  
Nada Milosevic ◽  
...  

BackgroundTumour-associated macrophages (TAM) play an important role in mediating tumour progression. In pancreatic cancer, infiltrating macrophages have been identified not only in invasive tumours, but also in early preinvasive pancreatic intraepithelial neoplasias and are known to mediate tumour progression.MethodsWe aimed to study the impact of pharmacological macrophage depletion by liposomal clodronate in the genetic mouse model of pancreatic cancer (KPC mouse: LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre). KPC mice were treated with liposomal clodronate or control liposomes from week 8 to week 20. Tumour and metastasis formation as well as alterations in local and circulating immune cells and cytokines were analysed.ResultsTreatment with liposomal clodronate effectively reduced CD11b-positive macrophages both in the pancreas and other organs such as liver, lung and spleen. Tumour incidence and size was only slightly reduced. However, metastasis formation in the liver und lungs was markedly diminished after macrophage depletion. Reduced macrophage count was associated with significant alterations in circulating growth factors and mediators known to be secreted by macrophages and associated with angiogenesis, most prominently VEGF. Moreover, application of liposomal clodronate led to marked alterations in circulating immune cells, among them reduced regulatory T cells.ConclusionsPharmacological depletion of macrophages in a genetic mouse model of pancreatic cancer markedly reduced metastasis formation and is associated with modulated profile of both secreted mediators and regulatory T cells. Pharmacological modulation of infiltrating macrophages represents a promising avenue for antimetastatic therapeutic approaches.


Author(s):  
Fuxiang Zhu ◽  
Aiting Wang ◽  
Yangyang Li ◽  
Rui Liang ◽  
Dan Li ◽  
...  

2016 ◽  
Vol 14 (6) ◽  
pp. 5556-5566 ◽  
Author(s):  
Yunhu Yu ◽  
Fang Cao ◽  
Qishan Ran ◽  
Xiaochuan Sun

Allergy ◽  
2018 ◽  
Vol 73 (9) ◽  
pp. 1801-1811 ◽  
Author(s):  
J. U. Shin ◽  
S. H. Kim ◽  
J. Y. Noh ◽  
J. H. Kim ◽  
H. R. Kim ◽  
...  

2008 ◽  
Vol 58 (4) ◽  
pp. 517-530 ◽  
Author(s):  
Robin Goforth ◽  
Aliasger K. Salem ◽  
Xiaoyan Zhu ◽  
Suzanne Miles ◽  
Xue-Qing Zhang ◽  
...  

2019 ◽  
Vol 15 (10) ◽  
pp. S123
Author(s):  
Anahita Jalilvand ◽  
Alecia Blaszczak ◽  
Sabrena Noria ◽  
Bradley Needleman ◽  
David Bradley ◽  
...  

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