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https://www.readbyqxmd.com/read/28926770/1-25-oh-2d3-induces-regulatory-t-cell-differentiation-by-influencing-the-vdr-plc-%C3%AE-1-tgf-%C3%AE-1-pathway
#1
Qiang Zhou, Shengying Qin, Jinyan Zhang, Lin Zhon, Zhihai Pen, Tonghai Xing
Vitamin D has been recommended as an immune modulator in recent years, in addition to regulating calcium-phosphorous-bone metabolism. Clinical studies on organ transplantation found that vitamin D sufficiency patients were less likely to develop acute cellular rejection within one year after transplantation compared to those with vitamin D deficiency. Thus, a high percentage of regulatory T cells might play a key role in preventing acute cellular rejection (ACR). In this report, we studied the specific effects of 1,25(OH)2D3 on human T cell diff ;erentiation, and determined the potential molecule mechanism behind...
September 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28924581/data-on-the-effects-of-eif6-downmodulation-on-the-proportions-of-innate-and-adaptive-immune-system-cell-subpopulations-and-on-thymocyte-maturation
#2
Nicola Manfrini, Sara Ricciardi, Annarita Miluzio, Maya Fedeli, Alessandra Scagliola, Simone Gallo, Thure Adler, Dirk H Busch, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabě de Angelis, Stefano Biffo
The data described in this article are related to "High levels of eukaryotic Initiation Factor 6 (eIF6) are required for immune system homeostasis and for steering the glycolytic flux of TCR-stimulated CD4(+) T cells in both mice and humans" (Manfrini et al., in press) [1]. eIF6 is a translation initiation factor required for ribosomal biogenesis (Sanvito et al., 1999) [2] and for proper translational initiation (Gallo and Manfrini, 2015; Miluzio et al., 2016) [3], [4] whose protein abundance requires tight regulation...
October 2017: Data in Brief
https://www.readbyqxmd.com/read/28924003/learning-the-high-dimensional-immunogenomic-features-that-predict-public-and-private-antibody-repertoires
#3
Victor Greiff, Cédric R Weber, Johannes Palme, Ulrich Bodenhofer, Enkelejda Miho, Ulrike Menzel, Sai T Reddy
Recent studies have revealed that immune repertoires contain a substantial fraction of public clones, which may be defined as Ab or TCR clonal sequences shared across individuals. It has remained unclear whether public clones possess predictable sequence features that differentiate them from private clones, which are believed to be generated largely stochastically. This knowledge gap represents a lack of insight into the shaping of immune repertoire diversity. Leveraging a machine learning approach capable of capturing the high-dimensional compositional information of each clonal sequence (defined by CDR3), we detected predictive public clone and private clone-specific immunogenomic differences concentrated in CDR3's N1-D-N2 region, which allowed the prediction of public and private status with 80% accuracy in humans and mice...
September 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28923982/emerging-concepts-in-tcr-specificity-rationalizing-and-maybe-predicting-outcomes
#4
REVIEW
Nishant K Singh, Timothy P Riley, Sarah Catherine B Baker, Tyler Borrman, Zhiping Weng, Brian M Baker
T cell specificity emerges from a myriad of processes, ranging from the biological pathways that control T cell signaling to the structural and physical mechanisms that influence how TCRs bind peptides and MHC proteins. Of these processes, the binding specificity of the TCR is a key component. However, TCR specificity is enigmatic: TCRs are at once specific but also cross-reactive. Although long appreciated, this duality continues to puzzle immunologists and has implications for the development of TCR-based therapeutics...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28919076/mitochondrial-priming-by-cd28
#5
Ramon I Klein Geltink, David O'Sullivan, Mauro Corrado, Anna Bremser, Michael D Buck, Joerg M Buescher, Elke Firat, Xuekai Zhu, Gabriele Niedermann, George Caputa, Beth Kelly, Ursula Warthorst, Anne Rensing-Ehl, Ryan L Kyle, Lana Vandersarren, Jonathan D Curtis, Annette E Patterson, Simon Lawless, Katarzyna Grzes, Jing Qiu, David E Sanin, Oliver Kretz, Tobias B Huber, Sophie Janssens, Bart N Lambrecht, Angelika S Rambold, Edward J Pearce, Erika L Pearce
T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand...
September 1, 2017: Cell
https://www.readbyqxmd.com/read/28918288/th9-cells-promote-antitumor-immunity-via-il-9-and-il-21-and-demonstrate-atypical-cytokine-expression-in-breast-cancer
#6
Fa-Ping You, Jian Zhang, Tao Cui, Rui Zhu, Chong-Qing Lv, Hai-Tao Tang, Di-Wen Sun
Breast cancer is a major cause of cancer-related death in women. Antitumor T cell responses play critical therapeutic roles, including direct cytotoxicity mediated by CD8(+) T cells and immunomodulatory roles mediated by CD4(+) T cells. The IL-9-expressing Th9 cells are recently found to present antitumor immunity in melanoma and lung adenocarcinoma. In this study, we found that IL-9 expression in the serum and in circulating CD4(+) T cells were significantly upregulated in breast cancer patients compared to healthy controls...
September 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28913674/prognostic-significance-of-corticotroph-staining-in-radiosurgery-for-non-functioning-pituitary-adenomas-a-multicenter-study
#7
Or Cohen-Inbar, Zhiyuan Xu, Cheng-Chia Lee, Chin-Chun Wu, Tomáš Chytka, Danilo Silva, Mayur Sharma, Hesham Radwan, Inga S Grills, Brandon Nguyen, Zaid Siddiqui, David Mathieu, Christian Iorio-Morin, Amparo Wolf, Christopher P Cifarelli, Daniel T Cifarelli, L Dade Lunsford, Douglas Kondziolka, Jason P Sheehan
Silent corticotroph staining pituitary adenoma (SCA) represents an uncommon subset of Non-Functioning adenomas (NFAs), hypothesized to be more locally aggressive. In this retrospective multicenter study, we investigate the safety and effectiveness of Stereotactic Radiosurgery (SRS) in patients with SCA compared with other non-SCA NFA's. Eight centers participating in the International Gamma-Knife Research Foundation (IGKRF) contributed to this study. Outcomes of 50 patients with confirmed SCAs and 307 patients with confirmed non-SCA NFA's treated with SRS were evaluated...
September 14, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28904128/integration-of-kinase-and-calcium-signaling-at-the-level-of-chromatin-underlies-inducible-gene-activation-in-t-cells
#8
Ruth Brignall, Pierre Cauchy, Sarah L Bevington, Bethany Gorman, Angela O Pisco, James Bagnall, Christopher Boddington, William Rowe, Hazel England, Kevin Rich, Lorraine Schmidt, Nigel P Dyer, Mark A Travis, Sascha Ott, Dean A Jackson, Peter N Cockerill, Pawel Paszek
TCR signaling pathways cooperate to activate the inducible transcription factors NF-κB, NFAT, and AP-1. In this study, using the calcium ionophore ionomycin and/or PMA on Jurkat T cells, we show that the gene expression program associated with activation of TCR signaling is closely related to specific chromatin landscapes. We find that calcium and kinase signaling cooperate to induce chromatin remodeling at ∼2100 chromatin regions, which demonstrate enriched binding motifs for inducible factors and correlate with target gene expression...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28903331/the-antigenic-identity-of-human-class-i-mhc-phosphopeptides-is-critically-dependent-upon-phosphorylation-status
#9
Fiyaz Mohammed, Daniel H Stones, Angela L Zarling, Carrie R Willcox, Jeffrey Shabanowitz, Kara L Cummings, Donald F Hunt, Mark Cobbold, Victor H Engelhard, Benjamin E Willcox
Dysregulated post-translational modification provides a source of altered self-antigens that can stimulate immune responses in autoimmunity, inflammation, and cancer. In recent years, phosphorylated peptides have emerged as a group of tumour-associated antigens presented by MHC molecules and recognised by T cells, and represent promising candidates for cancer immunotherapy. However, the impact of phosphorylation on the antigenic identity of phosphopeptide epitopes is unclear. Here we examined this by determining structures of MHC-bound phosphopeptides bearing canonical position 4-phosphorylations in the presence and absence of their phosphate moiety, and examining phosphopeptide recognition by the T cell receptor (TCR)...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902773/reduced-tcr-signalling-contributes-to-impaired-th17-responses-in-tolerant-kidney-transplant-recipients
#10
Estefania Nova-Lamperti, Marco Romano, Sofia Christakoudi, Manohursingh Runglall, Reuben McGregor, Paula Mobillo, Yogesh Kamra, Tjir-Li Tsui, Sonia Norris, Susan John, Dominic A Boardman, Robert I Lechler, Giovanna Lombardi, Maria P Hernandez-Fuentes
BACKGROUND: The development of spontaneous kidney transplant tolerance has been associated with numerous B cell-related immune alterations. We have previously shown that tolerant recipients exhibit reduced B cell receptor (BCR) signalling and higher IL-10 production than healthy volunteers. However, it is unclear whether CD4T cells from tolerant recipients also display an antiinflammatory profile that could contribute to graft maintenance. METHODS: CD4T cells were isolated from kidney transplant recipients who were identified as being tolerant recipients, patients with chronic-rejection or healthy volunteers...
September 12, 2017: Transplantation
https://www.readbyqxmd.com/read/28900926/immunological-disorders-regulation-of-ca-2-signaling-in-t-lymphocytes
#11
Sonal Srikanth, Jin Seok Woo, Zuoming Sun, Yousang Gwack
Engagement of T cell receptors (TCRs) with cognate antigens triggers cascades of signaling pathways in helper T cells. TCR signaling is essential for the effector function of helper T cells including proliferation, differentiation, and cytokine production. It also modulates effector T cell fate by inducing cell death, anergy (nonresponsiveness), exhaustion, and generation of regulatory T cells. One of the main axes of TCR signaling is the Ca(2+)-calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900678/socs1-regulator-of-t-cells-in-autoimmunity-and-cancer
#12
Subburaj Ilangumaran, Diwakar Bobbala, Sheela Ramanathan
SOCS1 is a negative feedback regulator of cytokine and growth factor receptor signaling, and plays an indispensable role in attenuating interferon gamma signaling. Studies on SOCS1-deficient mice have established a crucial role for SOCS1 in regulating CD8(+) T cell homeostasis. In the thymus, SOCS1 prevents thymocytes that had failed positive selection from surviving and expanding, ensures negative selection and prevents inappropriate developmental skewing toward the CD8 lineage. In the periphery, SOCS1 not only controls production of T cell stimulatory cytokines but also attenuates the sensitivity of CD8(+) T cells to synergistic cytokine stimulation and antigen non-specific activation...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900149/assessment-of-t-cell-receptor-repertoire-and-clonal-expansion-in-peripheral-t-cell-lymphoma-using-rna-seq-data
#13
Qiang Gong, Chao Wang, Weiwei Zhang, Javeed Iqbal, Yang Hu, Timothy C Greiner, Adam Cornish, Jo-Heon Kim, Raul Rabadan, Francesco Abate, Xin Wang, Giorgio G Inghirami, Timothy W McKeithan, Wing C Chan
T-cell clonality of peripheral T-cell lymphoma (PTCL) is routinely evaluated with a PCR-based method using genomic DNA. However, there are limitations with this approach. The purpose of this study was to determine the utility of RNA-seq for assessing T-cell clonality and T-cell antigen receptor (TCR) repertoire of the neoplastic T-cells in 108 PTCL samples. TCR transcripts, including complementarity-determining region 3 (CDR3) sequences, were assessed. In normal T cells, the CDR3 sequences were extremely diverse, without any clonotype representing more than 2% of the overall TCR population...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899359/transcript-profiling-of-the-immunological-interactions-between-actinobacillus-pleuropneumoniae-serotype-7-and-the-host-by-dual-rna-seq
#14
Ping Li, Zhiwen Xu, Xiangang Sun, Yue Yin, Yi Fan, Jun Zhao, Xiyu Mao, Jianbo Huang, Fan Yang, Ling Zhu
BACKGROUND: The complexity of the pathogenic mechanism underlying the host immune response to Actinobacillus pleuropneumonia (App) makes the use of preventive measures difficult, and a more global view of the host-pathogen interactions and new insights into this process are urgently needed to reveal the pathogenic and immune mechanisms underlying App infection. Here, we infected specific pathogen-free Mus musculus with App serotype 7 by intranasal inoculation to construct an acute hemorrhagic pneumonia infection model and isolated the infected lungs for analysis of the interactions by dual RNA-seq...
September 12, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28894547/a-novel-therapy-for-cocaine-dependence-during-abstinence-a-randomized-clinical-trial
#15
Bijan Pirnia, Ali Reza Moradi, Kambiz Pirnia, Parisa Kolahi, Rasool Roshan
BACKGROUND: Topiramate is an anticonvulsant drug and an ideal candidate for reducing the craving in people relying on cocaine. Contingency management is one of the common therapies in the domain of addiction. OBJECTIVE: The present study aimed to evaluate and compare three medication methods of Topiramate (TPM), Contingency Management (CM) and the combined TPM treatment and cash intervention on craving during abstinence. METHODS: This randomized clinical trial was conducted at Bijan Center for Substance Abuse Treatment in Tehran, Iran, from December 15, 2014 to November 20, 2015...
July 2017: Electronic Physician
https://www.readbyqxmd.com/read/28894001/intestinal-type-1-regulatory-t-cells-migrate-to-periphery-to-suppress-diabetogenic-t-cells-and-prevent-diabetes-development
#16
Hua Yu, Nicola Gagliani, Harumichi Ishigame, Samuel Huber, Shu Zhu, Enric Esplugues, Kevan C Herold, Li Wen, Richard A Flavell
Growing insight into the pathogenesis of autoimmune diseases and numerous studies in preclinical models highlights the potential of regulatory T cells to restore tolerance. By using non-obese diabetic (NOD) BDC2.5 TCR-transgenic (Tg), and IL-10 and Foxp3 double-reporter mice, we demonstrate that alteration of gut microbiota during cohousing experiments or treatment with anti-CD3 mAb significantly increase intestinal IL-10-producing type 1 regulatory T (Tr1) cells and decrease diabetes incidence. These intestinal antigen-specific Tr1 cells have the ability to migrate to the periphery via a variety of chemokine receptors such as CCR4, CCR5, and CCR7 and to suppress proliferation of Th1 cells in the pancreas...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28893902/the-cytosolic-domain-of-t-cell-receptor-%C3%AE-associates-with-membranes-in-a-dynamic-equilibrium-and-deeply-penetrates-the-bilayer
#17
Kerstin Zimmermann, Rebecca Eells, Frank Heinrich, Stefanie Rintoul, Brian Josey, Prabhanshu Shekhar, Mathias Lösche, Lawrence J Stern
Interactions between lipid bilayers and the membrane-proximal regions of membrane-associated proteins play important roles in regulat-ing membrane protein structure and function. The T-cell antigen receptor (TCR) is an assembly of eight single-pass membrane-spanning subunits on the surface of T-lymphocytes that initiates cytosolic signaling cascades upon binding antigens presented by MHC-family proteins on antigen-presenting cells. Its ζ subunit contains multiple cytosolic immunoreceptor tyrosine-based activation motifs (ITAMs) involved in signal transduction, and this subunit by itself is sufficient to couple extracellular stimuli to intracellular signaling events...
September 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28891256/composition-and-variation-analysis-of-the-tcr-%C3%AE-chain-cdr3-repertoire-in-neonatal-sepsis
#18
Jinqiao Sun, Bijun Sun, Yanyan Gao, Fusheng He, Lin Yang, Mingbang Wang, Wenhao Zhou
T cell receptor (TCR) diversity is clearly related to protection from infection. However, the characteristics of TCR diversity in neonates are not clear. In this study, we investigated the TCR diversity of neonates with sepsis. Twenty neonates with severe sepsis and 8 matched neonates without infection were enrolled in the study. For the neonates with sepsis, EDTA-anticoagulated blood was collected on day 1 after the diagnosis of sepsis and on day 7 of treatment. For the neonates without infection, blood was collected one time...
September 11, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28891065/il4-induced-gene-1-is-secreted-at-the-immune-synapse-and-modulates-tcr-activation-independently-of-its-enzymatic-activity
#19
Aude Aubatin, Nouhoum Sako, Xavier Decrouy, Emmanuel Donnadieu, Valérie Molinier-Frenkel, Flavia Castellano
Amino-acid catabolizing enzymes produced by mononuclear phagocytes play a central role in regulating the immune response. The mammalian phenylalanine-catabolizing enzyme IL4-induced gene 1 (IL4I1) inhibits effector T lymphocyte proliferation and facilitates regulatory T-cell development. IL4I1 expression by macrophages of various human tumors may affect patient prognosis as it facilitates tumor escape from the T-cell response in murine models. Its enzymatic activity appears to participate in its effects, but some actions of IL4I1 remain unclear...
September 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28889989/the-tnf-receptor-superfamily-nf-%C3%AE%C2%BAb-axis-is-critical-to-maintain-effector-regulatory-t-cells-in-lymphoid-and-non-lymphoid-tissues
#20
Ajithkumar Vasanthakumar, Yang Liao, Peggy Teh, Maria F Pascutti, Anna E Oja, Alexandra L Garnham, Renee Gloury, Jessica C Tempany, Tom Sidwell, Eloy Cuadrado, Paul Tuijnenburg, Taco W Kuijpers, Najoua Lalaoui, Lisa A Mielke, Vanessa L Bryant, Philip D Hodgkin, John Silke, Gordon K Smyth, Martijn A Nolte, Wei Shi, Axel Kallies
After exiting the thymus, Foxp3(+) regulatory T (Treg) cells undergo further differentiation in the periphery, resulting in the generation of mature, fully suppressive effector (e)Treg cells in a process dependent on TCR signaling and the transcription factor IRF4. Here, we show that tumor necrosis factor receptor superfamily (TNFRSF) signaling plays a crucial role in the development and maintenance of eTreg cells. TNFRSF signaling activated the NF-κB transcription factor RelA, which was required to maintain eTreg cells in lymphoid and non-lymphoid tissues, including RORγt(+) Treg cells in the small intestine...
September 4, 2017: Cell Reports
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