scholarly journals The short-term high fat diet-induced increase in %5-methylcytosine expression in peripheral blood T lymphocytes, is attenuated by low-dose aspirin

2019 ◽  
Author(s):  
Tinashe Mutize ◽  
Phiwayinkosi V. Dludla ◽  
Zibusiso Mkandla ◽  
Bongani B. Nkambule
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
High Fat Diet ◽  
Low Dose ◽  
High Fat ◽  
Short Term ◽  
Dose Aspirin ◽  
Low Dose Aspirin

AbstractObjectiveTo assess peripheral lymphocyte DNA methylation profiles in prediabetes using a high fat-diet-fed C57BL/6 animal model. We further evaluated whether low dose-aspirin, or low-dose aspirin in combination with metformin, could modulate global DNA methylation levels in peripheral blood lymphocytes.MethodsTwenty-eight (28) male C57BL/6 mice were used in two experimental phases. The first experiment involved animals (n=16) which were randomised to receive a low-fat diet (LFD) or high-fat diet (HFD) (n = 8/group) for 10 weeks. Whereas in the second experiment, HFD-fed mice (n=15) were randomised into 3 treatment groups, a low-dose aspirin (LDA), LDA and metformin group, and a clopidogrel group. DNA methylation profiles of were determined using flow cytometry.ResultsThe HFD group showed moderate weight gain and elevated postprandial blood glucose levels when compared to the LFD group after 2 weeks of HFD-feeding (p < 0.05). Interestingly, the HFD group had elevated levels of T cells expressing high levels %5-methylcytosine (p<0, 05). Notably, these elevated levels were lowered by short-term low-dose aspirin treatment.DiscussionT cells are involved in the propagation of the inflammatory response. Persistent T cell activation promotes chronic inflammation and insulin resistance. Low-dose aspirin may be effective in modulating T cell-specific global methylation.

Elevated T-helper 2 cytokine levels in high fat diet-fed C57BL/6 mice are attenuated by short-term 6-week treatment with a combination of low-dose aspirin and metformin

Cytokine ◽  
2020 ◽  
Vol 128 ◽  
pp. 154999 ◽  
Author(s):  
Thabsile J. Mahlangu ◽  
Phiwayinkosi V. Dludla ◽  
Vuyolwethu Mxinwa ◽  
Zibusiso Mkandla ◽  
Luca Tiano ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Low Dose ◽  
T Helper ◽  
High Fat ◽  
Short Term ◽  
T Helper 2 ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Cytokine Levels

scholarly journals Differential expression of glycoprotein IV on monocyte subsets following high-fat diet feeding and the impact of short-term low-dose aspirin treatment

2020 ◽  
Vol 7 ◽  
pp. 100047
Author(s):  
Kabelo Mokgalaboni ◽  
Phiwayinkosi V. Dludla ◽  
Zibusiso Mkandla ◽  
Tinashe Mutize ◽  
Tawanda Maurice Nyambuya ◽  
...  
Keyword(s):  
Differential Expression ◽  
High Fat Diet ◽  
Low Dose ◽  
Monocyte Subsets ◽  
High Fat ◽  
Short Term ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
The Impact

Abstract MP05: The Mechanism Of The Pvat Pro-inflammatory Micro-environment Formation During The Development Of High Fat Diet-induced Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yining Jin ◽  
Omar Kana ◽  
Ramya Kumar ◽  
Rance Nault ◽  
Hannah Garver ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
High Fat Diet ◽  
Cell Activation ◽  
Control Diet ◽  
Rna Seq ◽  
High Fat ◽  
Induced Hypertension ◽  
Th17 Differentiation

There is considerable evidence for a causative role for T cells in hypertension, including studies with immunosuppressive drugs and T cell-deficient models. Our previous studies showed that soluble mediators from mesenteric perivascular adipose tissue (mPVAT) modulate T cell function. Specifically, conditioned media from mPVAT (mPVAT-CM) from Dahl S rats on a high fat diet (HFD) promoted expression of the pro-inflammatory cytokines, IFNg, IL-17a and GM-CSF, by activated T cells. Furthermore, the Dahl S rats on HFD will later develop hypertension. Hypothesis: mPVAT is stimulated to produce immunomodulatory mediators that promotes Th1/17 differentiation preceding the development of HFD-induced hypertension. We conducted bulk RNA-seq on activated splenocytes cultured in mPVAT-CM from Dahl S rats on either control or HFD for 10 weeks. In accordance with our previous studies, PVAT-CM from HFD-fed rats significantly upregulated many genes associated with IFNg/IL-17 induction, including Mpeg1, Lyz2 and Tnfsf4 (5.0±1.78, 3.70±0.53 and 1.78±0.42 fold over Control diet, respectively). In contrast, Th2/Treg-associated genes, such as Ctla2a (-0.27±0.02) and Ccr4 (-0.41±0.03) were downregulated. We also performed single cell (sc) RNA-seq on the PVAT stromal vascular fraction (SVF) and found that acute inflammatory genes were enriched in the HFD group. Together with the bulk RNA-seq on mPVAT, these data strongly suggest that the pro-inflammatory mPVAT micro-environment may promote Th1/Th17 differentiation. To identify mediators in PVAT-CM that may induce Th1/Th17 differentiation, we compared the bulk RNA-seq on splenocytes cultured in PVAT-CM with bulk RNA-seq conducted on the whole mPVAT itself. We found that a T cell co-stimulatory receptor DPP4 (CD26), which is closely associated with T cell activation was significantly increased in mPVAT from HFD-fed rats (33.4±2.3 HFD vs. 15.3±1.8 Control diet). We also observed an increase in DPP4 global expression from mPVAT SVF in HFD-fed rats, as determined by scRNA-seq. Conclusion: The data suggest that HFD promotes the IFNg and IL-17a pathways in PVAT, which precedes hypertension in Dahl S rats and correlates with an increase in expression of DPP-4, a gene that promotes T cell activation. (NIH P01 HL070687).

scholarly journals High-fat diet-induced hypertension is associated with a proinflammatory T cell profile in male and female Dahl salt-sensitive rats

2018 ◽  
Vol 315 (6) ◽  
pp. H1713-H1723 ◽  
Author(s):  
Lia E. Taylor ◽  
Ellen E. Gillis ◽  
Jacqueline B. Musall ◽  
Babak Baban ◽  
Jennifer C. Sullivan
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
High Fat Diet ◽  
Female Rats ◽  
Male Rats ◽  
High Fat ◽  
Male And Female ◽  
The Impact ◽  
Cell Profile

Evidence supports a sex difference in the impact of a high-fat diet (HFD) on cardiovascular outcomes, with male experimental animals exhibiting greater increases in blood pressure (BP) than female experimental animals. The immune system has been implicated in HFD-induced increases in BP, and there is a sex difference in T-cell activation in hypertension. The goal of this study was to determine the impact of HFD on BP and aortic and renal T cell profiles in male and female Dahl salt-sensitive (DSS) rats. We hypothesized that male DSS rats would have greater increases in BP and T cell infiltration in response to a HFD compared with female DSS rats. BP was measured by tail-cuff plethysmography, and aortic and renal T cells were assessed by flow cytometric analysis in male and female DSS rats on a normal-fat diet (NFD) or HFD from 12 to 16 wk of age. Four weeks of HFD increased BP in male and female DSS rats to a similar degree. Increases in BP were accompanied by increased percentages of CD4+ T cells and T helper (Th)17 cells in both sexes, although male rats had more proinflammatory T cells. Percentages of renal CD3+ and CD4+ T cells as well as Th17 cells were increased in both sexes by the HFD, although the increase in CD3+ T cells was greater in male rats. HFD also decreased the percentage of aortic and renal regulatory T cells in both sexes, although female rats maintained more regulatory T cells than male rats regardless of diet. In conclusion, both male and female DSS rats exhibit BP sensitivity to a HFD; however, the mechanisms mediating HFD-induced increases in BP may be distinct as male rats exhibit greater increases in the percentage of proinflammatory T cells than female rats. NEW & NOTEWORTHY Our study demonstrates that male and female Dahl salt-sensitive rats exhibit similar increases in blood pressure to a high-fat diet and an increase in aortic and renal T cells. These results are in contrast to studies showing that female rats remain normotensive and/or upregulate regulatory T cells in response to hypertensive stimuli compared with male rats. Our data suggest that a 4-wk high-fat diet has sex-specific effects on the T cell profile in Dahl salt-sensitive rats.

Preliminary Study on the Abnormal DNA Methylation in T Cells from the Patients with Immune Related Pancytopenia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5156-5156
Author(s):  
Zonghong Shao ◽  
Yue Ren ◽  
Rong Fu
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
T Cell ◽  
Mrna Expression ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Mrna Level ◽  
Cd4 T Cell ◽  
Global Dna Methylation ◽  
Normal Controls

Abstract Objective To explore the global DNA methylation and the expression of regulatory genes for methylation in CD4 + T cells of the patients with immune related pancytopenia (IRP) and explore the role of methylation in pathogenesis of IRP. Methods Thirty IRP patients (untreated, n=15; remission, n=15) and 15 healthy donors as controls were enrolled from December 2012 to December 2013. CD4+ T cells were sorted by immunomagnetic separation. The global DNA methylation was tested with enzyme-linked immunosorbent assay (ELISA). The mRNA levels of DNA methylation-related regulating genes, DNA methyltransferases (DNMTs) and methylated CpG binding proteins (MBDs), were measured by real-time quantitative polymerase chain reaction (RT-PCR). Results The level of global DNA methylation in peripheral blood CD4+ T cells of untreated IRP patients (3.525%±2.046%)and remission patients (4.790%±1.471%) were significantly lower than that of normal controls (10.101%±3.449%) respectively (both P<0.05). DNMT3b mRNA level of untreated IRP patients (1.332±0.785) was significantly lower than that of normal controls (2.077±1.059) in CD4+T cells (P<0.05). The mRNA expression of MBD2 was significantly higher in CD4+ T cells from untreated and remission IRP patients (2.999±1.601, 2.055±1.576) than that in controls (0.581±0.247) (both P<0.05). The MBD4 mRNA level was significantly higher in CD4+ T cells from untreated IRP patients (2.736±2.719) compared to that in normal controls (1.167±1.006) (p<0.05). DNMT3b mRNA expression and CD4+ T cell DNA methylation to be positive correlated within IRP patients (r=0.569, p<0.01). The MBD2 mRNA expression negatively correlated with CD4+ T cell DNA methylation and the ratio of Th1/Th2 (r=-0.763, p<0.001; r = -0.652, p<0.05). The global methylation of CD4+ T cells negatively related to the ratio of CD5+ B cells (r= -0.439, p<0.05). Conclusions The globe DNA hypomethylation and abnormal expression of DNA methylation-related enzymes in peripheral blood CD4+ T cells may be related with the pathogenesis of IRP. Disclosures No relevant conflicts of interest to declare.

CD4+ T-cell immunity predicts long-lasting antitumor immunity after PD-1 blockade therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2545-2545
Author(s):  
Kyoichi Kaira ◽  
Ou Yamaguchi ◽  
Kenichi Yoshimura ◽  
Atsuto Mouri ◽  
Ayako Shiono ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Therapy Response ◽  
T Cell Immunity ◽  
Prediction Formula ◽  
Short Term ◽  
Peripheral Blood Mononuclear ◽  
Cell Immunity

2545 Background: Patients treated with programmed cell death 1 (PD-1)-blockade therapy fall into 3 distinct subgroups: non-responders presenting early disease progression, long survivors who achieve durable disease control, and the remaining short-term responders. We reported that the prediction formula comprised of the percentages of CD62L-downregulated (CD62Llow) and CD25+FOXP3+CD4+T cells in the peripheral blood predicted non-responders of non-small cell lung cancer patients (n = 50) scheduled to receive anti-PD-1-antibody (nivolumab) therapy in the 2017 ASCO meeting. In this study, we included 171 patients with NSCLC who were scheduled for nivolumab treatment after obtaining written informed consent. Peripheral blood mononuclear cells (PBMC) were examined before and after Nivolumab therapy up to 2 years to investigate the differences between long survivors and short-term responders. Methods: The patients received Nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks. Tumor response was assessed with the use of the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, at week 8 and every 8 weeks thereafter. PBMCs were analyzed with a 18-color microfluorometer, LSR Fortessa and a masscytometer, CyTOF. Results: The responder-type patient group whose prediction formula values were greater than 192 showed significantly longer PFS ( P< 0.0001) and OS ( P< 0.0001). The long survivors who consisted of tail plateau of PFS exhibited significantly more CD62LlowCD4+T cells than the short-term responders as pre-existing immunity. The remaining responders kept significantly higher percentages of CD62LlowCD4+T cells ( P= 0.0088) and prediction formula values ( P= 0.017) than the patients with acquired resistance. Conclusions: The pre-existing CD4+T cell balance between primed effector and regulatory T cells correlated with anti-PD-1 therapy response. Further, CD62Llowcell-dominant CD4+T cell immunity was required to maintain durable antitumor reactivity induced by anti-PD-1 antibody therapy. These results have important clinical implication, as they support anti-PD-1 therapy provision to all potentially responding patients and pave the way for new treatment strategies for patients with distinct CD4+T cell immune statuses. Clinical trial information: UMIN000020719.

scholarly journals A High-Fat Diet Containing 50% Egg-Phosphatidylcholine Increased the Proportion of T Cells Expressing a Memory Marker in Male Wistar Rats

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1140-1140
Author(s):  
Tianna Rusnak ◽  
Jessy Azarcoya Barrera ◽  
Bethany Wollin ◽  
Anna Thomsen ◽  
Alexander Makarowski ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Dose Effect ◽  
Helper T Cells ◽  
High Fat ◽  
Low Fat ◽  
Male Wistar Rats ◽  
Egg Pc

Abstract Objectives Studies have suggested that high-fat (HF) diets are associated with immune dysfunction, which results in a lower production of IL-2 and a lower proportion of helper T cells. Providing a diet containing 100% phosphatidylcholine (PC), a form of choline mainly found in eggs, has been shown to increase IL-2 production early in life. However, this is of no relevance for human consumption since no human diet will contain 100% PC. Therefore, the objective of this study was to determine the dose effect of egg-PC added to a high fat diet compared to a control high fat and low fat diets on T cell function in male Wistar rats. Methods At four weeks of age, male Wistar rats were randomized to consume one of 6 diets: 1- Control low fat (CLF, 10%wt/wt fat, 100% free choline (FC), n = 10); 2- Control high fat (CHF, 25% wt/wt fat, 100% FC, n = 10); 3- 100% PCHF (100PCHF, 25% wt/wt fat, 100% PC, n = 10); 4- 75% PCHF (75PCHF, 25% wt/wt fat, 75% PC, 25% FC, n = 10); 5- 50% PCHF (50PCHF, 25% wt/wt fat, 50% PC, 50% FC, n = 10); 6- 25% PCHF (25PCHF; 25% wt/wt fat, 25% PC, 75% FC, n = 10). Fatty acid composition was closely matched in all of the diets. Anthropometric data was collected through the duration of the study (12 weeks). At the end of the study, splenocytes phenotypes were measured by flow cytometry. Results From week 1 to week 10 there was no difference in body weight between the diets. Starting from week 2 the CLF group had a higher food intake compared to the other groups. The 50PCHF diet had a higher proportion of helper T cells (CD4+) compared to the CLF and CHF diets. In addition, 50PCHF had a higher proportion of helper T cells expressing IL-2 receptors (CD4+CD25+) compared to 25PCHF (P &lt; 0.05). 50PCHF also had a higher proportion of T cells expressing a memory marker (CD3+CD27+) compared with all HF diets (all P &lt; 0.05) but not the CLF diet. Conclusions Our results suggest that a diet providing 50% of total choline in the form of egg-PC normalizes the proportion of T cells expressing CD27 in the context of a HF diet which may lead to a better immune response if a second exposure to a pathogen occurs. Whether the higher proportion of helper T cells expressing the IL-2 receptor in the 50PCHF group is associated with better T cell response upon challenge remains to be investigated. Funding Sources Egg farmers of Canada, NSERC.

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