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T cell regulation

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https://www.readbyqxmd.com/read/29334376/positively-selected-enhancer-elements-endow-osteosarcoma-cells-with-metastatic-competence
#1
James J Morrow, Ian Bayles, Alister P W Funnell, Tyler E Miller, Alina Saiakhova, Michael M Lizardo, Cynthia F Bartels, Maaike Y Kapteijn, Stevephen Hung, Arnulfo Mendoza, Gursimran Dhillon, Daniel R Chee, Jay T Myers, Frederick Allen, Marco Gambarotti, Alberto Righi, Analisa DiFeo, Brian P Rubin, Alex Y Huang, Paul S Meltzer, Lee J Helman, Piero Picci, Henri Versteeg, John Stamatoyannopolus, Chand Khanna, Peter C Scacheri
Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumorigenesis. Here, we investigate the contribution of enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic profiling, we identify substantial differences in enhancer activity between primary and metastatic human tumors and between near isogenic pairs of highly lung metastatic and nonmetastatic osteosarcoma cell lines. We term these regions metastatic variant enhancer loci (Met-VELs)...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334374/transitory-presence-of-myeloid-derived-suppressor-cells-in-neonates-is-critical-for-control-of-inflammation
#2
Yu-Mei He, Xing Li, Michela Perego, Yulia Nefedova, Andrew V Kossenkov, Erik A Jensen, Valerian Kagan, Yu-Feng Liu, Shu-Yu Fu, Qing-Jian Ye, Yan-Hong Zhou, Lai Wei, Dmitry I Gabrilovich, Jie Zhou
Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions. Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics. No or very few MDSCs are observed in steady-state physiological conditions. Therefore, until recently, accumulation of MDSCs was considered a consequence of pathological processes or pregnancy...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29333726/calcium-current-properties-in-dystrophin-deficient-ventricular-cardiomyocytes-from-aged-mdx-mice
#3
Lena Rubi, Hannes Todt, Helmut Kubista, Xaver Koenig, Karlheinz Hilber
Duchenne muscular dystrophy (DMD), caused by mutations in the gene encoding for the cytoskeletal protein dystrophin, is linked with severe cardiac complications including cardiomyopathy development and cardiac arrhythmias. We and others recently reported that currents through L-type calcium (Ca) channels were significantly increased, and channel inactivation was reduced in dystrophin-deficient ventricular cardiomyocytes derived from the mdx mouse, the most commonly used animal model for human DMD. These gain-of-function Ca channel abnormalities may enhance the risk of Ca-dependent arrhythmias and cellular Ca overload in the dystrophic heart...
January 2018: Physiological Reports
https://www.readbyqxmd.com/read/29331730/exenatide-exerts-cognitive-effects-by-modulating-the-bdnf-trkb-neurotrophic-axis-in-adult-mice
#4
Manuela Bomba, Alberto Granzotto, Vanessa Castelli, Noemi Massetti, Elena Silvestri, Lorella M T Canzoniero, Annamaria Cimini, Stefano L Sensi
Modulation of insulin-dependent signaling is emerging as a valuable therapeutic tool to target neurodegeneration. In the brain, the activation of insulin receptors promotes cell growth, neuronal repair, and protection. Altered brain insulin signaling participates in the cognitive decline seen in Alzheimer's disease patients and the aging brain. Glucagon-like peptide-1 (GLP-1) regulates insulin secretion and, along with GLP-1 analogues, enhances neurotrophic signaling and counteracts cognitive deficits in preclinical models of neurodegeneration...
December 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29331376/microrna-425-facilitates-pathogenic-th17-cell-differentiation-by-targeting-forkhead-box-o1-foxo1-and-is-associated-with-inflammatory-bowel-disease
#5
Xue Yang, Qinyu He, Zhenzhen Guo, Fei Xiong, Yi Li, Yan Pan, Caiping Gao, Liangping Li, Chong He
Inflammatory bowel disease (IBD) is a chronic autoimmune disease, and its pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as a crucial regulator of autoimmune diseases. In this study, we demonstrated, for the first time, that miR-425 was significantly up-regulated in peripheral blood mononuclear cells (PBMC) and mucosa of patients with IBD. In note, T helper (Th) 17 cells were found to be the major source of miR-425 expression. Using gain-of-function approaches, we demonstrated that miR-425 could facilitate the differentiation of CD4+ T cells into Th17 lineage...
January 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29331373/establishment-and-characterization-of-five-immortalized-human-scalp-dermal-papilla-cell-lines
#6
Mi Hee Kwack, Jung Min Yang, Gong Hee Won, Moon Kyu Kim, Jung Chul Kim, Young Kwan Sung
Dermal papilla (DP) regulates the growth and cycling of hair follicles. Cultured DP cells are useful for the study of their role in relation to hair growth and regeneration. However, cultivation of human DP cells is tedious and difficult. In addition, cultured DP cells possess a relatively short replicative life span, requiring immortalized human DP cell lines. We previously established an immortalized human DP cell line, SV40T-hTERT-DPC, by introducing human telomerase reverse transcriptase (hTERT) gene into the transformed cell line, SV40T-DPC...
January 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29331367/molecular-characterization-and-differential-expression-analysis-of-interleukin-1%C3%AE-from-ovis-aries
#7
Yi-Ming Shui, Shi-Ying Lu, Xing Guo, Xi-Lin Liu, Bao-Quan Fu, Pan Hu, Lin-Lin Qu, Nan-Nan Liu, Yan-Song Li, Lu-Lu Wang, Fei-Fei Zhai, Dan-Di Ju, Zeng-Shan Liu, Yu Zhou, Hong-Lin Ren
The interleukin-1 family is an important component of the innate immune system and plays an important role in regulating immune responses on the invasion of intracellular parasites in the acquired immune system. Interleukin 1β (IL-1β) is one of the members of the IL-1 family that predominantly activates downstream signaling pathways to play immunological functions of stimulating T and B lymphocyte activation and promoting the various syntheses of inflammatory substances in conjunction with other cytokines...
January 10, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#8
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29331322/expression-level-of-risk-genes-of-mhc-class-ii-is-a-susceptibility-factor-for-autoimmunity-new-insights
#9
REVIEW
Carmen Gianfran, Laura Pisapia, Stefania Picascia, Maria Strazzullo, Giovanna Del Pozzo
To date, the study of the impact of major hystocompatibility complex on autoimmunity has been prevalently focused on structural diversity of MHC molecules in binding and presentation of (auto)antigens to cognate T cells. Recently, a number of experimental evidences suggested new points of view to investigate the complex relationships between MHC gene expression and the individual predisposition to autoimmune diseases. Irrespective of the nature of the antigen, a threshold of MHC-peptide complexes needs to be reached, as well as a threshold of T cell receptors engaged is required, for the activation and proliferation of autoantigen-reactive T cells...
January 10, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29331291/global-microrna-profiling-in-human-bone-marrow-skeletal-stromal-or-mesenchymal-stem-cells-identified-candidates-for-bone-regeneration
#10
Chi-Chih Chang, Morten T Venø, Li Chen, Nicholas Ditzel, Dang Q S Le, Philipp Dillschneider, Moustapha Kassem, Jørgen Kjems
Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem cells) during in vitro osteoblast differentiation. We functionally validated the regulatory effects of several miRNAs on osteoblast differentiation and identified 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis...
December 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29331036/prognostic-significance-of-mir-21-and-pdcd4-in-patients-with-stage-ii-esophageal-carcinoma-after-surgical-resection
#11
Jiandong Zhang, Lei Ma, Daimeng Shi, Zhen Zhang, Chuanshan Yao, Xulin Zhao, Quanxiao Xu, Penghao Wen, Limin He
Many studies have shown that randomized clinical trial with long-term follow-up found no improvement in stage II esophageal carcinoma (EC) patients receiving preoperative neoadjuvant chemoradiotherapy or chemotherapy treatment, this limitation underscored the urgent need for novel and reliable biomarkers for prognosis and prediction in stage II EC. miR-21 is frequently over-expressed while programmed cell death 4 (PDCD4) is often down-regulated in solid tumors. This study aimed to investigate the clinicopathological and prognostic significance of miR-21 and PDCD4 expression and to elucidate any correlation between miR-21 and PDCD4 expression in stage II EC patients...
January 13, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29330785/genetic-knockdown-and-pharmacologic-inhibition-of-hypoxia-inducible-factor-hif-hydroxylases
#12
Christina Pickel, Cormac T Taylor, Carsten C Scholz
Reduced oxygen supply that does not satisfy tissue and cellular demand (hypoxia) regularly occurs both in health and disease. Hence, the capacity for cellular oxygen sensing is of vital importance for each cell to be able to alter its energy metabolism and promote adaptation to hypoxia. The hypoxia-inducible factor (HIF) prolyl hydroxylases 1-3 (PHD1-3) and the asparagine hydroxylase factor-inhibiting HIF (FIH) are the primary cellular oxygen sensors, which confer cellular oxygen-dependent sensitivity upon HIF as well as other hypoxia-sensitive pathways, such as nuclear factor κB (NF-κB)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330484/single-cell-rna-sequencing-resolves-self-antigen-expression-during-mtec-development
#13
Ricardo J Miragaia, Xiuwei Zhang, Tomás Gomes, Valentine Svensson, Tomislav Ilicic, Johan Henriksson, Gozde Kar, Tapio Lönnberg
The crucial capability of T cells for discrimination between self and non-self peptides is based on negative selection of developing thymocytes by medullary thymic epithelial cells (mTECs). The mTECs purge autoreactive T cells by expression of cell-type specific genes referred to as tissue-restricted antigens (TRAs). Although the autoimmune regulator (AIRE) protein is known to promote the expression of a subset of TRAs, its mechanism of action is still not fully understood. The expression of TRAs that are not under the control of AIRE also needs further characterization...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330322/cutting-edge-piezo1-mechanosensors-optimize-human-t-cell-activation
#14
Chinky Shiu Chen Liu, Deblina Raychaudhuri, Barnali Paul, Yogaditya Chakrabarty, Amrit Raj Ghosh, Oindrila Rahaman, Arindam Talukdar, Dipyaman Ganguly
TCRs recognize peptides on MHC molecules and induce downstream signaling, leading to activation and clonal expansion. In addition to the strength of the interaction of TCRs with peptides on MHC molecules, mechanical forces contribute to optimal T cell activation, as reflected by the superior efficiency of immobilized TCR-cross-linking Abs compared with soluble Abs in TCR triggering, although a dedicated mechanotransduction module is not identified. We found that the professional mechanosensor protein Piezo1 is critically involved in human T cell activation...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29330296/tumor-progression-is-mediated-by-thymosin-%C3%A3-4-through-a-tgf%C3%A3-mrtf-signaling-axis
#15
Tsuyoshi Morita, Kenichiro Hayashi
Although enhanced thymosin beta-ß4 (TMSBX4/Tß4) expression is associated with tumor progression and metastasis, its tumor-promoting functions remain largely unknown. Here it is demonstrated that transforming growth factor beta (TGFß) facilitates Tß4 expression and leads to the activation of myocardin-related transcription factors (MRTFs), which are co-activators of serum response factor (SRF) and regulate the expression of genes critical for the epithelial-mesenchymal transition (EMT) and tumor metastasis...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330147/genetic-ablation-of-rbm38-promotes-lymphomagenesis-in-the-context-of-mutant-p53-by-downregulating-pten
#16
Jin Zhang, Enshun Xu, Cong Ren, Hee Jung Yang, Yanhong Zhang, Wenqiang Sun, Xiangmudong Kong, Weici Zhang, Mingyi Chen, Eric C Huang, Xinbin Chen
Mutant p53 exerts gain-of-function effects that drive metastatic progression and therapeutic resistance, but the basis for these effects remain obscure. The RNA binding protein RBM38 limits translation of mutant p53 and is often ablated in tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer susceptibility in mutant p53 knock-in mice, by shortening lifespan, altering tumor incidence and promoting T cell lymphomagenesis. Loss of Rbm38 enhanced mutant p53 expression and decreased expression of the tumor suppressor Pten, a key regulator of T cell development...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29330144/kindlin-1-promotes-pulmonary-breast-cancer-metastasis
#17
Sana Sarvi, Hitesh Patel, Jun Li, Georgia L Dodd, Helen Creedon, Morwenna Muir, Jocelyn Ward, John C Dawson, Martin Lee, Jayne Culley, Donald M Salter, Andrew H Sims, Adam Byron, Valerie G Brunton
In breast cancer, increased expression of the cytoskeletal adaptor protein Kindlin-1 has been linked to increased risks of lung metastasis, but the functional basis is unknown. Here we show that in a mouse model of polyomavirus middle T antigen-induced mammary tumorigenesis, loss of Kindlin-1 reduced early pulmonary arrest and later development of lung metastasis. This phenotype relied on the ability of Kindlin-1 to bind and activate β integrin heterodimers. Kindlin-1 loss reduced α4 integrin-mediated adhesion of mammary tumor cells to the adhesion molecule VCAM-1 on endothelial cells...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29329973/altered-gene-expression-in-tree-shrew-retina-and-retinal-pigment-epithelium-produced-by-short-periods-of-minus-lens-wear
#18
Li He, Michael R Frost, John T Siegwart, Thomas T Norton
Hyperopic refractive error is detected by retinal neurons, which generate GO signals through a direct emmetropization signaling cascade: retinal pigment epithelium (RPE) into choroid and then into sclera, thereby increasing axial elongation. To examine signaling early in this cascade, we measured gene expression in the retina and RPE after short exposure to hyperopia produced by minus-lens wear. Gene expression in each tissue was compared with gene expression in combined retina + RPE. Starting 24 days after normal eye opening, three groups of juvenile tree shrews (n = 7 each) wore a monocular -5 D lens...
January 9, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29329543/stat3-induced-lncrna-haglros-overexpression-contributes-to-the-malignant-progression-of-gastric-cancer-cells-via-mtor-signal-mediated-inhibition-of-autophagy
#19
Jin-Fei Chen, Peng Wu, Rui Xia, Jian Yang, Xin-Ying Huo, Dong-Ying Gu, Cui-Ju Tang, Wei De, Fen Yang
BACKGROUND: Long noncoding RNAs (lncRNAs) are an important class of functional regulators involved in human cancers development, including gastric cancer (GC). Studying aberrantly expressed lncRNAs may provide us with new insights into the occurrence and development of gastric cancer by acting as oncogenes or tumor suppressors. In this study, we aim to examine the expression pattern of lncRNA HAGLROS in GC and its clinical significance as well as its biological role in tumor progression...
January 12, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29329251/pharmacological-investigation-of-the-anti-inflammation-and-anti-oxidation-activities-of-diallyl-disulfide-in-a-rat-emphysema-model-induced-by-cigarette-smoke-extract
#20
Yan Liu, Ang Li, Xiuli Feng, Xiao Sun, Xiaosong Zhu, Zhongxi Zhao
Diallyl disulfide (DADS) is the main organosulfur ingredient in garlic, with known antioxidant and anti-inflammatory activities. The aim of the present study was to investigate the effect of DADS on reducing the inflammation and redox imbalance in a rat emphysema model that was induced by intraperitoneal injection of cigarette smoke extract (CSE). Briefly, DADS exerted an anti-inflammation effect on emphysema rats through decreasing cell influx in the bronchoalveolar lavage fluid (BALF) and suppressing pro-inflammation cytokine production including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) via inhibiting the NF-κB pathway...
January 12, 2018: Nutrients
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