Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue

AbstractThis exploratory retrospective study aims to investigate the thermal changes in the thyroid gland region of patients with hypothyroidism and fibromyalgia by analyzing the temperature of the brown adipose tissue (BAT). A total of 166 individuals from 1000 thermographic electronic medical records were classified into four groups: Group HP + FM-50 individuals with hypothyroidism and fibromyalgia; Group FM-56 individuals with fibromyalgia only; Group HP-30 individuals with hypothyroidism only, and Group Control-30 healthy individuals. The thermal images from the electronic medical records were acquired by a FLIR T650SC infrared camera (used for thermometry) and the temperature data for each group were statistically analyzed. Group HP + FM showed r = 0, meaning that the average temperatures of the thyroid and BAT are independent of each other. Groups FM, HP and Control showed r = 1, meaning that the average temperatures of the thyroid and BAT were directly related. Our findings showed that the average temperatures of the thyroid and BAT regions are similar. Also, there was no correlation between thyroid gland temperature and the presence of hypothyroidism or fibromyalgia using thermometry.

Download Full-text

Effects of cold acclimation on lipid metabolism in adipose tissue

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1961.200.4.847 ◽

1961 ◽

Vol 200 (4) ◽

pp. 847-850 ◽

Cited By ~ 82

Author(s):

Judith K. Patkin ◽

E. J. Masoro

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Fatty Acid ◽

Lipid Metabolism ◽

Cold Acclimation ◽

Long Chain Fatty Acids ◽

Synthetic Capacity ◽

And Control ◽

Long Chain ◽

Chain Fatty Acids

Cold acclimation is known to alter hepatic lipid metabolism. Liver slices from cold-acclimated rats have a greatly depressed capacity to synthesize long-chain fatty acids from acctate-1-C14. Since adipose tissue is the major site of lipogenic activity in the intact animal, its fatty acid synthetic capacity was studied. In contrast to the liver, it was found that adipose tissue from the cold-acclimated rat synthesized three to six times as much long-chain fatty acids per milligram of tissue protein as the adipose tissue from the control rat living at 25°C. Evidence is presented indicating that adipose tissue from cold-acclimated and control rats esterify long-chain fatty acids at the same rate. The ability of adipose tissue to oxidize palmitic acid to CO2 was found to be unaltered by cold acclimation. The fate of the large amount of fatty acid synthesized in the adipose tissue of cold-acclimated rats is discussed.

Download Full-text

Epicardial Adipose Tissue as a Source of Nuclear Factor-κB and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2579 ◽

2009 ◽

Vol 94 (1) ◽

pp. 261-267 ◽

Cited By ~ 71

Author(s):

A. R. Baker ◽

A. L. Harte ◽

N. Howell ◽

D. C. Pritlove ◽

A. M. Ranasinghe ◽

...

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery Disease ◽

Adipose Tissue ◽

Coronary Artery ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Toll Like Receptor ◽

Inflammatory Profile ◽

Artery Disease ◽

And Control

Abstract Context: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated. Objectives: The objectives of the study were to: 1) examine key mediators of the nuclear factor-κB (NFκB) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects. Design: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies. Results: Western blotting showed epicardial AT had significantly higher NFκB, inhibitory-κB kinase (IKK)-γ, IKKβ, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-α. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 ± 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 ± 0.57 EU/ml; P<0.05]. Conclusion: Epicardial AT from patients with CAD shows increased NFκB, IKKβ, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFκB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.

Download Full-text

Bcl11b prevents fatal autoimmunity by promoting Treg cell program and constraining innate lineages in Treg cells

Science Advances ◽

10.1126/sciadv.aaw0480 ◽

2019 ◽

Vol 5 (8) ◽

pp. eaaw0480 ◽

Cited By ~ 4

Author(s):

Theodore T. Drashansky ◽

Eric Helm ◽

Zhiguang Huo ◽

Nina Curkovic ◽

Preet Kumar ◽

...

Keyword(s):

Transcription Factor ◽

Steady State ◽

Treg Cell ◽

Nk Cell ◽

Treg Cells ◽

Chromatin Accessibility ◽

Peripheral Tolerance ◽

Identity Control ◽

And Function ◽

Human And Mouse

Regulatory T (Treg) cells are essential for peripheral tolerance and rely on the transcription factor (TF) Foxp3 for their generation and function. Several other TFs are critical for the Treg cell program. We found that mice deficient in Bcl11b TF solely in Treg cells developed fatal autoimmunity, and Bcl11b-deficient Treg cells had severely altered function. Bcl11b KO Treg cells showed decreased functional marker levels in homeostatic conditions, inflammation, and tumors. Bcl11b controlled expression of essential Treg program genes at steady state and in inflammation. Bcl11b bound to genomic regulatory regions of Treg program genes in both human and mouse Treg cells, overlapping with Foxp3 binding; these genes showed altered chromatin accessibility in the absence of Bcl11b. Additionally, Bcl11b restrained myeloid and NK cell programs in Treg cells. Our study provides new mechanistic insights on the Treg cell program and identity control, with major implications for therapies in autoimmunity and cancer.

Download Full-text

Immunological effect of irreversible electroporation on solid tumors

10.21203/rs.3.rs-121118/v1 ◽

2020 ◽

Author(s):

Xiaoxia Guo ◽

Fang Du ◽

Qin Liu ◽

Yan Guo ◽

Qingbing Wang ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Nk Cells ◽

Irreversible Electroporation ◽

Treg Cells ◽

T Cell Subsets ◽

Activated T Cells ◽

Immunological Effect ◽

Immunological Effects ◽

And Control

Abstract Background This study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE). Methods We evaluated the systemic immune response in patients with hepatocellular carcinoma (HCC) after IRE treatment. Furthermore, we analyzed the tumor infiltrating T lymphocytes and the level of serum cytokines in IRE and control groups of tumor-bearing mice. Results We observed that IRE induced an increase in WBC, neutrophil and monocyte counts and a decrease in lymphocyte count 1 day post-IRE and returned to baseline values within 7 days in the patients. Meanwhile, circulating CD4+ T cell subsets, but not CD8+, decreased 1 day post-IRE. The activated T cells and natural killer (NK) cells increased, and regulatory T (Treg) cells decreased. Furthermore, a significant increase in cytotoxic CD8+ T cells infiltration was observed on ablative tumors in mice. The level of serum IFN-γ also significantly increased in the IRE group. Conclusions Our study demonstrated that IRE not only induced immediate innate immune response dominated by the increase of neutrophils, monocytes and NK cells, but also upregulated activated T cells and downregulated Treg. Meanwhile, the results from the animal model indicated that IRE could induce antitumor adaptive immunity dominated by cytotoxic CD8+ T cells.

Download Full-text

Dysbiosis of Gut Microbiota and Its Relationship with the Regulatory T Cells in Patients with Aplastic Anemia

10.21203/rs.3.rs-147288/v1 ◽

2021 ◽

Author(s):

Mengxiao Ren ◽

Yongqin Ge ◽

Jindan Qi ◽

Shengli Xue ◽

Miao Miao ◽

...

Keyword(s):

Gut Microbiota ◽

Aplastic Anemia ◽

Treg Cell ◽

Relative Abundance ◽

Treg Cells ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Cell Counts ◽

And Control ◽

Healthy Participants

Abstract Background: The characteristics of gut microbiota (GM) and its relationship with the Regulatory T Cells (Treg) remains unclear in patients with aplastic anemia (AA). Methods: This study was a cross-sectional survey which included 12 AA patients consisted of 6 with severity aplastic anemia (SAA) and 6 with non-severity aplastic anemia (NSAA) and 6 healthy participants. The GM and its relationship with the Treg cells of AA patients were analyzed. Results: The results showed that the presence of compositional differences in the GM structure between the AA and Control groups. The bacterial communities were depleted of Clostridia class (e.g., Lachnospiraceae ND3007, Lachnospiraceae XPB1014, Lachnolostridium, Ruminococcaceae UCG 013 and Butyricicoccus genus) in AA group, especially in SAA group. Inversely, the relative abundance of Lactobacillus and Streptococcus genus from Bacilli class were increased significantly in patients with SAA. The relative abundance of Lachnospiraceae (r=0.663, p=0.029), Clostridiaceae 1 (r=0.619, p=0.042) and Clostridiales vadinBB60 group family (r=0.674, p=0.023) which from Clostridia class, were positively correlated with the Treg cell counts. Conclusion: We speculated that the decrease of some bacteria from Clostridia class may participate in the pathophysiological process of AA through reducing the Treg cell counts. Notwithstanding the low sample size, our data provided some clues that the treatment strategy of AA could start by adjusting the imbalance of GM, increasing Treg cell counts to improve the suppression of bone marrow hematopoiesis.

Download Full-text

The effect of a synbiotic on blood biochemistry and concentrations of leptin, ghrelin and their receptors in prepubertal rats consuming a diet containing excessive fat

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2019.04.64-71 ◽

2019 ◽

pp. 64-71

Author(s):

Г.А. Дроздова ◽

О.И. Линецкая ◽

Е.А. Нургалеева ◽

Э.И. Эткина ◽

Э.Ф. Аглетдинов

Keyword(s):

Adipose Tissue ◽

Serum Level ◽

Lipid Profile ◽

Gastrointestinal Microbiota ◽

Ghrelin Receptor ◽

Leptin Receptors ◽

Fat Consumption ◽

Excessive Consumption ◽

Ghrelin Receptors ◽

And Control

Цель работы - изучить возможности патогенетической коррекции синбиотиком метаболических нарушений, вызванных чрезмерным потреблением жиров и оценить уровень лептина, грелина и их рецепторов. Методика. В работе использовалось второе поколение лабораторных крыс линии Вистар препубертатного возраста, находившихся на диете с избыточным содержанием жиров (51% от общего рациона). В возрасте 5 нед. в рацион экспериментальной подгруппы включали синбиотик, по достижению 7-недельного возраста животных выводили из эксперимента декапитацией с последующим забором материала для бактериологических, биохимических и иммуноферментных исследований. Результаты. Показано, что избыточное потребление жиров способствует росту условно-патогенной микробиоты, снижению содержания лакто- и бифидобактерий в толстом кишечнике и развитию дислипидемии. Наблюдается статистически значимое повышение уровня лептина в сыворотке крови на 49,9 %. В жировой ткани отмечено увеличение количества рецепторов к лептину ( в два раза) и грелину (на 28,2%). После коррекции синбиотиком положительная динамика отмечалась со стороны микробиоты, липидного профиля, снижался уровень лептина в сыворотке крови и рецепторов к грелину в жировой ткани. Заключение: синбиотик способствует нормализации микробиоты желудочно-кишечного тракта, липидного профиля и уровня пептидных гормонов, ответственных за чувство голода и насыщения. The aim of the study was to evaluate a possibility of using synbiotics for pathogenetic correction of metabolic disorders induced by excessive consumption of fat and to measure levels of leptin, ghrelin, and their receptors. Methods. Experiments were conducted on the second generation of prepubertal Wistar rats consuming a diet with excessive fat (51% of diet). A synbiotic was included into the diet of a rat group aged 5 weeks. At age of 7 weeks, animals of the experimental and control groups were decapitated and samples were taken for bacteriological, biochemical, and enzyme immunoassay studies. Results. Excessive fat consumption resulted in growth of conditionally pathogenic microbiota, decreased levels of lacto- and bifidobacteria in the large intestine and feces, and development of dyslipidemia. Also, serum level of leptin was increased by 49.9%, ghrelin receptor density in adipose tissue was increased by 28.2%, and leptin receptors density in adipose tissue was increased twofold. The synbiotic treatment resulted in beneficial changes of the microbiota and lipid profile; serum level of leptin and ghrelin receptors density in adipose tissue decreased. Conclusion: The synbiotic drug normalized the gastrointestinal microbiota, lipid profile, and peptide hormones responsible for feelings of hunger and satiety.

Download Full-text

Fatty Acid Ethyl Esters in Liver and Adipose Tissues as Postmortem Markers for Ethanol Intake

Clinical Chemistry ◽

10.1093/clinchem/47.4.722 ◽

2001 ◽

Vol 47 (4) ◽

pp. 722-725 ◽

Cited By ~ 19

Author(s):

Raneem O Salem ◽

Majed A Refaai ◽

Joanne E Cluette-Brown ◽

Joshua W Russo ◽

Michael Laposata

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Normal Saline ◽

Ethanol Intake ◽

Fatty Acid Ethyl Esters ◽

Ethyl Esters ◽

Ethanol Ingestion ◽

Adipose Tissues ◽

Tissue Samples ◽

And Control

Abstract Background: Fatty acid ethyl esters (FAEEs) are nonoxidative metabolites of ethanol. FAEEs are found in liver, pancreas, and adipose tissues up to 24 h after consumption of ethanol, and on that basis, they are potentially useful markers for ethanol intake. In this study with rats, we investigated the efficacy of using FAEEs in liver and in adipose tissue as postmortem markers for premortem ethanol ingestion. Methods: An animal study was conducted in which test rats received injections of ethanol and control rats received injections of normal saline. The rats were killed 2 h after the injections. The bodies of the animals were stored at 4 °C up to 12 h, and samples of liver and adipose tissues were collected at different time intervals and processed for FAEE quantification. In another set of experiments, the rats received injections and were killed as described above, but bodies of animals from both groups were stored at 4, 25, or 37 °C for up to 72 h, and liver samples were collected and processed for FAEE quantification. Results: FAEEs were detected up to 12 h after death in liver and adipose tissue samples from the bodies of ethanol-treated animals stored at 4 °C; negligible amounts were detected in the bodies of animals that received normal saline. Adipose tissues contained higher amounts of FAEEs than liver, as well as more species: eight FAEE species in adipose tissue and five in liver tissue. Higher concentrations of FAEEs were detected in livers of treated animals stored at 25 °C for up to 48 h than in livers of controls stored under the same conditions. Conclusions: For at least 12 h after death, FAEEs in liver and adipose tissues are useful postmortem markers of premortem ethanol ingestion.

Download Full-text