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T cell signaling

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https://www.readbyqxmd.com/read/28102541/tgf-%C3%AE-regulation-of-encephalitogenic-and-regulatory-t-cells-in-multiple-sclerosis
#1
REVIEW
Priscilla W Lee, Mary E Severin, Amy E Lovett-Racke
Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine that has been shown to influence the differentiation and function of T cells. The role that TGF-β plays in immune-mediated disease, such as multiple sclerosis (MS), has become a major area of investigation since CD4(+) T cells appear to be a major mediator of autoimmunity. This review provides an analysis of the literature on the role that TGF-β plays in the generation and regulation of encephalitogenic and regulatory T cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, as well as in T cells of MS patients...
January 19, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28102226/chronic-lymphocytic-leukaemia
#2
Thomas J Kipps, Freda K Stevenson, Catherine J Wu, Carlo M Croce, Graham Packham, William G Wierda, Susan O'Brien, John Gribben, Kanti Rai
Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5(+) B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all...
January 19, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28102193/tumour-derived-interleukin-35-promotes-pancreatic-ductal-adenocarcinoma-cell-extravasation-and-metastasis-by-inducing-icam1-expression
#3
Chongbiao Huang, Na Li, Zengxun Li, Antao Chang, Yanan Chen, Tiansuo Zhao, Yang Li, Xiuchao Wang, Wei Zhang, Zhimin Wang, Lin Luo, Jingjing Shi, Shengyu Yang, He Ren, Jihui Hao
Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28101959/comprehensive-analysis-of-transcript-changes-associated-with-allograft-rejection-combining-universal-and-selective-features
#4
Philip F Halloran, Jeffery M Venner, Konrad S Famulski
We annotated the top transcripts associated with kidney transplant rejection by p-value, either universal for all rejection or selective for T cell-mediated (TCMR) or antibody-mediated rejection (ABMR). We used eight class comparison algorithms to interrogate microarray results from 703 biopsies, 205 with rejection. The positive comparators were all rejection, TCMR, or ABMR; the negative comparators varied from normal biopsies to all non-rejecting biopsies, including other diseases. The universal algorithm, rejection vs...
January 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28101891/different-expression-of-leptin-and-igf1-in-the-adult-and-prepubertal-testis-in-dogs
#5
L Müller, M P Kowalewski, I M Reichler, E Kollár, O Balogh
Leptin (Lep) and insulin-like growth factor 1 (IGF1) are implicated in the regulation of testicular function, but in dogs, our knowledge is limited to the possible role of the IGF1 system in testicular tumours. In this study, we aimed to describe and compare gene expression and protein localization of Lep, IGF1 and their receptors (LepR and IGF1R, respectively) in the testis of healthy adult and prepubertal dogs. Testes were collected from sexually healthy mature (n = 7) and from 8-week-old dogs (n = 7)...
January 18, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28101184/anti-inflammatory-effects-of-luteolin-on-experimental-autoimmune-thyroiditis-in-mice
#6
Nan Xia, Gang Chen, Min Liu, Xiaozhen Ye, Yahui Pan, Jiuyu Ge, Yanting Mao, Hongwei Wang, Jian Wang, Sijing Xie
Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease and is believed to be a predominately T cell-mediated autoimmunity. Signal transducer and activator of transcription (STAT)3 is a crucial transcription factor of T cell-mediated immunity, with key roles in the proliferation and migration of T helper (Th) cells, differentiation of Th cells into Th17 cells, and the balance between Treg cells and Th17 cells. Flavonoid luteolin has been shown to markedly inhibit Tyr705 activation/phosphorylation of STAT3 and exert anti-inflammatory effects in multiple sclerosis...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100849/the-role-genes-encoding-of-killer-cell-immunoglobulin-like-receptors-kirs-and-their-ligands-in-susceptibility-to-and-progression-of-hiv-infection
#7
Olga Błachowicz, Katarzyna Zwolińska
NK cells are a part of the innate antiviral response. Their activity is regulated by signals from the surface receptors. Some of them, known as killer cell immunoglobulin-like receptors (KIRs), determine the quality and intensity of the immunological response, together with their ligands (HLA class I). KIR genes are very polymorphic, and this is reflected in the NK activity modulation. The stimulation of NK cells, especially in the early stages of the infection, can reduce the transmission of HIV or slow down the progression of infection...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100838/car-t-cells-engage-in-anticancer-martial-arts
#8
Saar Gill
A clever redesign of the chimeric antigen receptor T cell concept turns a cancer-mediated immunosuppressive cytokine into a growth signal.
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28100678/modulation-of-naive-cd8-t-cell-response-features-by-ligand-density-affinity-and-continued-signaling-via-internalized-tcrs
#9
Renu Balyan, Rupali Gund, Chitra Ebenezer, Jasneet Kaur Khalsa, Divya Anna Verghese, Thyagarajan Krishnamurthy, Anna George, Vineeta Bal, Satyajit Rath, Ashutosh Chaudhry
T cell response magnitudes increase with increasing antigenic dosage. However, it is unclear whether ligand density only modulates the proportions of responding ligand-specific T cells or also alters responses at the single cell level. Using brief (3 h) exposure of TCR-transgenic mouse CD8 T cells in vitro to varying densities of cognate peptide-MHC ligand followed by ligand-free culture in IL-2, we found that ligand density determined the frequencies of responding cells but not the expression levels of the early activation marker molecule, CD69...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28100666/t-type-ca2-channels-are-required-for-enhanced-sympathetic-axon-growth-by-tnf%C3%AE-reverse-signalling
#10
Lilian Kisiswa, Clara Erice, Laurent Ferron, Sean Wyatt, Catarina Osório, Annette C Dolphin, Alun M Davies
Tumour necrosis factor receptor 1 (TNFR1)-activated TNFα reverse signalling, in which membrane-integrated TNFα functions as a receptor for TNFR1, enhances axon growth from developing sympathetic neurons and plays a crucial role in establishing sympathetic innervation. Here, we have investigated the link between TNFα reverse signalling and axon growth in cultured sympathetic neurons. TNFR1-activated TNFα reverse signalling promotes Ca(2+) influx, and highly selective T-type Ca(2+) channel inhibitors, but not pharmacological inhibitors of L-type, N-type and P/Q-type Ca(2+) channels, prevented enhanced axon growth...
January 2017: Open Biology
https://www.readbyqxmd.com/read/28100650/transforming-growth-factor-%C3%AE-suppresses-peroxisome-proliferator-activated-receptor-%C3%AE-expression-via-both-smad-binding-and-novel-tgf-%C3%AE-inhibitory-elements
#11
Sowmya P Lakshmi, Aravind T Reddy, Raju C Reddy
Transforming growth factor β (TGF-β) contributes to wound healing and, when dysregulated, to pathological fibrosis. TGF-β and the anti-fibrotic nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) repress each other's expression, and such PPARγ downregulation is prominent in fibrosis and mediated, via previously unknown mechanisms, by SMAD signaling. Here we show that TGF-β induces association of SMAD3 with both SMAD4, needed for translocation of the complex into the nucleus, and the essential context-sensitive corepressors E2F4 and p107...
January 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28100611/the-envelope-gene-of-transmitted-hiv-1-resists-a-late-ifn%C3%AE-induced-block
#12
Suzannah J Rihn, Toshana L Foster, Idoia Busnadiego, Muhamad Afiq Aziz, Joseph Hughes, Stuart J D Neil, Sam J Wilson
: Type I interferon (IFN) signaling engenders an antiviral state that likely plays an important role in constraining HIV-1 transmission and contributes to defining subsequent AIDS pathogenesis. Type II IFN (IFNγ) also induces an antiviral state but is often primarily considered to be an immunomodulatory cytokine. We report that IFNγ stimulation can induce an antiviral state that can be both distinct from that of type I interferon, and can potently inhibit HIV-1 in primary CD4+ T cells and a number of human cell lines...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100386/-effect-of-extracellular-signal-regulated-kinas-1-2-expression-and-hpv16-infection-and-their-interaction-in-progression-of-cervical-cancerization
#13
S L Fan, L Ding, Z Y Ren, X Chen, X S Sun, C C Li, C L Liu, W L Jia, Q L Li, J T Wang
Objective: To investigate the effect of ERK1/2 protein expression and HPV16 infection, as well as their interaction in the cervical carcinogenesis. Methods: A total of 176 patients, including 34 cases with normal cervix (NC), 26 cases with cervical intraepithelial neoplasm Ⅰ (CIN Ⅰ), 57 cases with cervical intraepithelial neoplasm Ⅱ/Ⅲ (CIN Ⅱ/Ⅲ) and 59 cases with cervical squamous cell carcinoma (SCC), were enrolled from Shanxi Tumor Hospital, Shanxi Maternal and Child Health Center, Jincheng Coal General Hospital from September 2013 to March 2014...
January 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28100240/reactivation-of-dormant-anti-tumor-immunity-a-clinical-perspective-of-therapeutic-immune-checkpoint-modulation
#14
REVIEW
Richard Greil, Evelyn Hutterer, Tanja Nicole Hartmann, Lisa Pleyer
In favor of their outgrowth, cancer cells must resist immune surveillance and edit the immune response. Cancer immunoediting is characterized by fundamental changes in the cellular composition and the inflammatory cytokine profiles in the microenvironment of the primary tumor and metastatic niches, with an ever increasing complexity of interactions between tumor cells and the immune system. Recent data suggest that genetic instability and immunoediting are not necessarily disparate processes. Increasing mutational load may be associated with multiple neoepitopes expressed by the tumor cells and thus increased chances for the immune system to recognize and combat these cells...
January 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28100106/systemic-lupus-erythematosus-in-the-light-of-the-regulatory-effects-of-galectin-1-on-t-cell-function
#15
Á Hornung, É Monostori, L Kovács
Galectin-1 is an endogenous immunoregulatory lectin-type protein. Its most important effects are the inhibition of the differentiation and cytokine production of Th1 and Th17 cells, and the induction of apoptosis of activated T-cells. Galectin-1 has been identified as a key molecule in antitumor immune surveillance, and data are accumulating about the pathogenic role of its deficiency, and the beneficial effects of its administration in various autoimmune disease models. Initial animal and human studies strongly suggest deficiencies in both galectin-1 production and responsiveness in systemic lupus erythematosus (SLE) T-cells...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28100093/p19-targeted-abd-derived-protein-variants-inhibit-il-23-binding-and-exert-suppressive-control-over-il-23-stimulated-expansion-of-primary-human-il-17-t-cells
#16
Lucie Křížová, Milan Kuchař, Hana Petroková, Radim Osička, Marie Hlavničková, Ondřej Pelák, Jiří Černý, Tomáš Kalina, Petr Malý
Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23...
January 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28100033/relaxin-3-inputs-target-hippocampal-interneurons-and-deletion-of-hilar-relaxin-3-receptors-in-floxed-rxfp3-mice-impairs-spatial-memory
#17
M Haidar, G Guèvremont, C Zhang, Rad Bathgate, E Timofeeva, C M Smith, A L Gundlach
Hippocampus is innervated by γ-aminobutyric acid (GABA) 'projection' neurons of the nucleus incertus (NI), including a population expressing the neuropeptide, relaxin-3 (RLN3). In studies aimed at gaining an understanding of the role of RLN3 signaling in hippocampus via its Gi/o -protein-coupled receptor, RXFP3, we examined the distribution of RLN3-immunoreactive nerve fibres and RXFP3 mRNA-positive neurons in relation to hippocampal GABA neuron populations. RLN3-positive elements were detected in close-apposition with a substantial population of somatostatin (SST)- and GABA-immunoreactive neurons, and a smaller population of parvalbumin- and calretinin-immunoreactive neurons in different hippocampal areas, consistent with the relative distribution patterns of RXFP3 mRNA and these marker transcripts...
January 18, 2017: Hippocampus
https://www.readbyqxmd.com/read/28100021/identifying-the-biphasic-role-of-calcineurin-nfat-signaling-enables-replacement-of-sox2-in-somatic-cell-reprogramming
#18
Sherif Khodeer, Takumi Era
Induction of pluripotency with defined factors (Oct4, Sox2, Klf4, c-Myc) raises hopes for successful clinical trials. Despite considerable efforts, the molecular mechanism of reprogramming remains poorly understood. The aim of the present study was to identify the role of calcineurin/nuclear factor of activated T cells (NFAT) in reprogramming. Our results demonstrated a biphasic role for calcineurin/NFAT signaling during reprogramming. In the early phase of reprogramming, calcineurin activity is required to maintain proper cell cycle division and for mesenchymal-epithelial transition...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28099945/in-vivo-and-in-vitro-effects-of-microrna-27a-on-proliferation-migration-and-invasion-of-breast-cancer-cells-through-targeting-of-sfrp1-gene-via-wnt-%C3%AE-catenin-signaling-pathway
#19
Ling-Yu Kong, Mei Xue, Qing-Cai Zhang, Chuan-Fu Su
This study aims to explore the effects of microRNA-27a (miR-27a) targeting of SFRP1 on the proliferation, migration and invasion of breast cancer (BC) cells through the regulation of Wnt/β-catenin signaling pathway. BC and normal breast tissues were obtained from 396 female BC patients and 308 female patients with benign breast lesions respectively. Human normal mammary epithelial (MCF-10A) and BC cell lines (BT-20, MCF-7, T-47D and MDA-MB-231) were cultured. After cell transfection, BC cells were assigned to six groups: control, miR-27a mimics, miR-27a inhibitors, negative control (NC), si-SFRP1 and si-SFRP1 + miR-27a inhibitors groups...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099934/tolfenamic-acid-induced-alterations-in-genes-and-pathways-in-pancreatic-cancer-cells
#20
Umesh T Sankpal, Steve Goodison, Michelle Jones-Pauley, Myrna Hurtado, Fan Zhang, Riyaz Basha
Non-steroidal anti-inflammatory drugs (NSAIDs) are being tested extensively for their role in the treatment and prevention of several cancers. Typically NSAIDs exhibit anti-tumor activities via modulation of cyclooxygenase (COX)-dependent mechanisms, however, an anti-cancer NSAID tolfenamic acid (TA) is believed to work through COX-independent pathways. Results from our laboratory and others have demonstrated the anti-cancer activity of TA in various cancer models including pancreatic cancer. TA has been shown to modulate certain cellular processes including, apoptosis, reactive oxygen species and signaling...
January 14, 2017: Oncotarget
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