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Regulatory t cells

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https://www.readbyqxmd.com/read/29240919/genome-wide-dose-dependent-inhibition-of-histone-deacetylases-studies-reveal-their-roles-in-enhancer-remodeling-and-suppression-of-oncogenic-super-enhancers
#1
Gilson J Sanchez, Phillip A Richmond, Eric N Bunker, Samuel S Karman, Joseph Azofeifa, Aaron T Garnett, Quanbin Xu, Graycen E Wheeler, Cathryn M Toomey, Qinghong Zhang, Robin D Dowell, Xuedong Liu
Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non-transformed cell line. Exposure to low nanomolar largazole concentrations (<GI50) predominantly resulted in upregulation of gene transcripts whereas higher largazole doses (≥GI50) triggered a general decrease in mRNA accumulation...
December 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29239725/t-cell-calcium-dynamics-visualized-in-a-ratiometric-tdtomato-gcamp6f-transgenic-reporter-mouse
#2
Tobias X Dong, Shivashankar Othy, Amit Jairaman, Jonathan Skupsky, Angel Zavala, Ian Parker, Joseph L Dynes, Michael D Cahalan
Calcium is an essential cellular messenger that regulates numerous functions in living organisms. Here we describe development and characterization of 'Salsa6f', a fusion of GCaMP6f and tdTomato optimized for cell tracking while monitoring cytosolic Ca2+, and a transgenic Ca2+ reporter mouse with Salsa6f targeted to the Rosa26 locus for Cre-dependent expression in specific cell types. The development and function of T cells was unaffected in Cd4-Salsa6f mice. We describe Ca2+ signals reported by Salsa6f during T cell receptor activation in naïve T cells, helper Th17 T cells and regulatory T cells, and Ca2+ signals mediated in T cells by an activator of mechanosensitive Piezo1channels...
December 14, 2017: ELife
https://www.readbyqxmd.com/read/29239722/calcium-mediated-shaping-of-naive-cd4-t-cell-phenotype-and-function
#3
Vincent Guichard, Nelly Bonilla, Aurélie Durand, Alexandra Audemard-Verger, Thomas Guilbert, Bruno Martin, Bruno Lucas, Cédric Auffray
Continuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced/peripheral regulatory T cells. To decipher the molecular mechanisms governing this process, we here focus on the TCR signaling cascade and demonstrate that a rise in intracellular calcium levels is sufficient to modulate the phenotype of mouse naive CD4 T cells and to increase their sensitivity to regulatory T-cell polarization signals, both processes relying on Calcineurin activation...
December 14, 2017: ELife
https://www.readbyqxmd.com/read/29239062/gvhd-amelioration-by-human-bone-marrow-mesenchymal-stromal-stem-cell-derived-extracellular-vesicles-is-associated-with-peripheral-preservation-of-naive-t-cell-populations
#4
Sumie Fujii, Yasuo Miura, Aya Fujishiro, Takero Shindo, Yutaka Shimazu, Hideyo Hirai, Hidetoshi Tahara, Akifumi Takaori-Kondo, Tatsuo Ichinohe, Taira Maekawa
A substantial proportion of patients with acute graft-versus-host disease (aGVHD) respond to cell therapy with culture-expanded human bone marrow mesenchymal stromal/stem cells (BM-MSCs). However, the mechanisms by which these cells can ameliorate aGVHD-associated complications remain to be clarified. We show here that BM-MSC-derived extracellular vesicles (EVs) recapitulated the therapeutic effects of BM-MSCs against aGVHD. Systemic infusion of human BM-MSC-derived EVs prolonged the survival of mice with aGVHD and reduced the pathologic damage in multiple GVHD-targeted organs...
December 14, 2017: Stem Cells
https://www.readbyqxmd.com/read/29238707/drug-repurposing-for-the-treatment-of-acute-myeloid-leukemia
#5
REVIEW
Vibeke Andresen, Bjørn T Gjertsen
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature myeloid progenitor cells in the bone marrow, compromising of normal blood cell production and ultimately resulting in bone marrow failure. With a 20% overall survival rate at 5 years and 50% in the 18- to 65-year-old age group, new medicines are needed. It is proposed that development of repurposed drugs may be a part of the new therapy needed. AML is subdivided into recurrent molecular entities based on molecular genetics increasingly accessible for precision medicine...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29238703/characterization-of-alpha-fetoprotein-effects-on-dendritic-cell-and-its-function-as-effector-immune-response-activator
#6
Jeremiah Suryatenggara, Heri Wibowo, Wahyuni Lukita Atmodjo, George Mathew
Tumor antigen alpha-fetoprotein (AFP) can promote immune tolerance toward tumor cells by inducing regulatory functions of the immune system. The purpose of this study was to characterize the effects of AFP on dendritic cells (DC) in their antitumor immune response stimulation and subsequent immune tolerance toward tumor cells. Monocytes were cultured in medium with GM-CSF and IL-4 and incubated for 6 days to generate immature DC (imDC). AFP was added into the treatment group at the beginning of the monocyte-derived DC culture...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/29238350/differentiation-and-transmigration-of-cd4-t-cells-in-neuroinflammation-and-autoimmunity
#7
REVIEW
Sandip Ashok Sonar, Girdhari Lal
CD4+ T cells play a central role in orchestrating protective immunity and autoimmunity. The activation and differentiation of myelin-reactive CD4+ T cells into effector (Th1 and Th17) and regulatory (Tregs) subsets at the peripheral tissues, and their subsequent transmigration across the blood-brain barrier (BBB) into the central nervous system (CNS) parenchyma are decisive events in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis. How the Th1, Th17, and regulatory Tregs transmigrate across the BBB into the CNS and cause CNS inflammation is not clearly understood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29238347/langerhans-cells-programmed-by-the-epidermis
#8
REVIEW
Kalum Clayton, Andres F Vallejo, James Davies, Sofia Sirvent, Marta E Polak
Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels. These cells determine the appropriate adaptive immune response (inflammation or tolerance) by interpreting the microenvironmental context in which they encounter foreign substances. In a normal physiological, "non-dangerous" situation, LCs coordinate a continuous state of immune tolerance, preventing unnecessary and harmful immune activation. Conversely, when they sense a danger signal, for example during infection or when the physical integrity of skin has been compromised as a result of a trauma, they instruct T lymphocytes of the adaptive immune system to mount efficient effector responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29238207/advances-in-t-cell-checkpoint-immunotherapy-for-head-and-neck-squamous-cell-carcinoma
#9
REVIEW
Xinmeng Qi, Bo Jia, Xue Zhao, Dan Yu
Head and neck squamous cell carcinoma (HNSCC) has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells "immune checkpoint" has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoints contribute to tumor immune escape through negative immune regulatory signals (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, etc)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29238018/-regulation-of-bone-by-il-17-producing-t-cells
#10
Kazuo Okamoto
  Bone is a component of the skeletal-locomotor system but also functions as an immunological organ that harbors hematopoietic stem and progenitor cells. Since the immune and skeletal systems are closely related through a number of shared regulatory molecules including cytokines and receptors, bone can be affected in various immune disorders. Rheumatoid arthritis is a typical disease in which the immune system affects the bone metabolism. The enhanced activity of osteoclasts by the activation of Th17 cells causes the joint destruction in rheumatoid arthritis...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29238015/-in-vivo-imaging-of-cutaneous-inflammation-novel-insights-into-cutaneous-immune-responses-revealed-by-multi-photon-microscopic-analysis
#11
Tetsuya Honda, Kenji Kabashima
  Skin is an outermost organ that serves as an interface between the host and the environment. The skin provides not only mechanical barrier functions, but also an active immunological barrier that provides the first line of defense against infections. For the effective clearance of pathogens or antigens in the skin, immune cells, especially effector T cells, must quickly exert their effector functions while avoiding the host damage by their excess activation. Therefore, the quality, magnitude, and the duration of the effector T cell activity must be carefully regulated...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29237778/mpges1-dependent-prostaglandin-e2-pge2-controls-antigen-specific-th17-and-th1-responses-by-regulating-t-autocrine-and-paracrine-pge2-production
#12
Damian Maseda, Elizabeth M Johnson, Lindsay E Nyhoff, Bridgette Baron, Fumiaki Kojima, Ashley J Wilhelm, Martin R Ward, Jerold G Woodward, David D Brand, Leslie J Crofford
The integration of inflammatory signals is paramount in controlling the intensity and duration of immune responses. Eicosanoids, particularly PGE2, are critical molecules in the initiation and resolution of inflammation and in the transition from innate to acquired immune responses. Microsomal PGE synthase 1 (mPGES1) is an integral membrane enzyme whose regulated expression controls PGE2 levels and is highly expressed at sites of inflammation. PGE2 is also associated with modulation of autoimmunity through altering the IL-23/IL-17 axis and regulatory T cell (Treg) development...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29237775/induction-of-immunosuppressive-cd8-cd25-foxp3-regulatory-t-cells-by-suboptimal-stimulation-with-staphylococcal-enterotoxin-c1
#13
Juyeun Lee, Nogi Park, Joo Youn Park, Barbara L F Kaplan, Stephen B Pruett, Juw Won Park, Yong Ho Park, Keun Seok Seo
Superantigens (SAgs) produced by Staphylococcus aureus at high concentrations induce proliferation of T cells bearing specific TCR Vβ sequences and massive cytokinemia that cause toxic shock syndrome. However, the biological relevance of SAgs produced at very low concentrations during asymptomatic colonization or chronic infections is not understood. In this study, we demonstrate that suboptimal stimulation of human PBMCs with a low concentration (1 ng/ml) of staphylococcal enterotoxin C1, at which half-maximal T cell proliferation was observed, induced CD8+CD25+ T cells expressing markers related to regulatory T cells (Tregs), such as IFN-γ, IL-10, TGF-β, FOXP3, CD28, CTLA4, TNFR2, CD45RO, and HLA-DR...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29237705/cilia-loss-sensitizes-cells-to-transformation-by-activating-the-mevalonate-pathway
#14
Yue-Zhen Deng, Zhen Cai, Shuo Shi, Hao Jiang, Yu-Rong Shang, Ning Ma, Jing-Jing Wang, Dong-Xian Guan, Tian-Wei Chen, Ye-Fei Rong, Zhen-Yu Qian, Er-Bin Zhang, Dan Feng, Quan-Li Zhou, Yi-Nan Du, Dong-Ping Liu, Xing-Xu Huang, Lu-Ming Liu, Eugene Chin, Dang-Sheng Li, Xiao-Fan Wang, Xue-Li Zhang, Dong Xie
Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, the roles of cilia in cell transformation are unknown. In this study, disrupted ciliogenesis was observed in cancer cells and pancreatic cancer tissues, which facilitated oncogene-induced transformation of normal pancreatic cells (HPDE6C7) and NIH3T3 cells through activating the mevalonate (MVA) pathway. Disruption of ciliogenesis up-regulated MVA enzymes through β catenin-T cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by β-catenin-TCF signaling was recapitulated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and human PDAC samples...
December 13, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29237160/hydrogen-treatment-protects-mice-against-chronic-pancreatitis-by-restoring-regulatory-t-cells-loss
#15
Luguang Chen, Chao Ma, Yun Bian, Jing Li, Tiegong Wang, Li Su, Jianping Lu
BACKGROUND/AIMS: Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive tissue destruction and fibrogenesis. The development of chronic pancreatitis is associated with immune cell dysregulation. Currently, the specific and effective treatment of chronic pancreatitis remains absent. METHODS: By using an L-arginine induced chronic pancreatitis mouse model, we tested the therapeutic potential of hydrogen, a strong hydroxyl radicals scavenger, in the chronic pancreatitis model...
December 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29237087/type-frequency-and-spatial-distribution-of-immune-cell-infiltrates-in-cns-germinomas-evidence-for-inflammatory-and-immunosuppressive-mechanisms
#16
Pia Zapka, Evelyn Dörner, Verena Dreschmann, Noriaki Sakamato, Glen Kristiansen, Gabriele Calaminus, Christian Vokuhl, Ivo Leuschner, Torsten Pietsch
Central nervous system germinomas are characterized by a massive immune cell infiltrate. We systematically characterized these immune cells in 28 germinomas by immunophenotyping and image analysis. mRNA expression was analyzed by Nanostring technology and in situ RNA hybridization. Tumor infiltrating lymphocytes (TILs) were composed of 61.8% ± 3.1% (mean ± SE) CD3-positive T cells, including 45.2% ± 3.5% of CD4-positive T-helper cells, 23.4% ± 1.5% of CD8-positive cytotoxic T cells, 5.5% ± 0...
December 11, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29236775/active-site-targeted-covalent-irreversible-inhibitors-of-usp7-impair-the-functions-of-foxp3-t-regulatory-cells-by-promoting-ubiquitination-of-tip60
#17
Feng Wang, Liqing Wang, Jian Wu, Ivan Sokirniy, Phuong Nguyen, Thomas Bregnard, Joseph Weinstock, Michael Mattern, Irina Bezsonova, Wayne W Hancock, Suresh Kumar
Accumulation of Foxp3+ T-regulatory (Treg) cells in the tumor microenvironment is associated with tumor immune evasion and poor patient outcome in the case of many solid tumors. Current therapeutic strategies for blocking Treg functions are not Treg-specific, and display only modest and transient efficacy. Recent studies revealed that ubiquitin-specific protease 7 (USP7) is essential for Treg functions by stabilizing expression of Tip60 and Foxp3, which together are central to the development and maintenance of the Treg cell lineage...
2017: PloS One
https://www.readbyqxmd.com/read/29235530/tri-microspheres-prevent-key-signs-of-dry-eye-disease-in-a-murine-inflammatory-model
#18
Michelle L Ratay, Stephen C Balmert, Abhinav P Acharya, Ashlee C Greene, Thiagarajan Meyyappan, Steven R Little
Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235284/-recent-research-progress-in-immunomodulatory-effects-of-chinese-herbal-medicine-on-asthma-treatment
#19
REVIEW
Fang-Fang Zhou, Zhao-Xia Xu, Aipire Adila, Jin-Yao Li
Asthma is a kind of chronic respiratory inflammation, commonly with breathlessness, chest tightness, coughing, recurrent episodes of wheezing and airflow obstruction, severely affecting human health. A variety of immunocytes are involved in this chronic disease. Chinese herbal medicine(CHM) has a long history in the treatment of asthma. A large number of studies have shown that CHM could ameliorate asthma symptoms through regulating cellular immune responses. This paper reviewed the studies of CHM on the regulation of immunocytes and their mechanisms in recent years, including the count of inflammatory cells, maturation of dendritic cells, balance of helper T cell subtypes, induction of regulatory T cells and intracellular signaling pathways...
October 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29235119/v-set-and-ig-domain-containing-4-vsig4-expressing-hepatic-f4-80-cells-regulate-oral-antigen-specific-responses-in-mouse
#20
Wonhwa Shin, Youkyoung Jeon, Inhak Choi, Yeon-Jeong Kim
Oral tolerance can prevent unnecessary immune responses against dietary antigens. Members of the B7 protein family play critical roles in the positive and/or negative regulation of T cell responses to interactions between APCs and T cells. V-set and Ig domain-containing 4 (VSIG4), a B7-related co-signaling molecule, has been known to act as a co-inhibitory ligand and may be critical in establishing immune tolerance. Therefore, we investigated the regulation of VSIG4 signaling in a food allergy and experimental oral tolerance murine models...
December 13, 2017: European Journal of Immunology
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