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T regulatory cells

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https://www.readbyqxmd.com/read/28742882/t-cell-intrinsic-tlr2-stimulation-promotes-il-10-expression-and-suppressive-activity-by-cd45rbhi-t-cells
#1
Janice C Jun, Mark B Jones, Douglas M Oswald, Edward S Sim, Amruth R Jonnalagadda, Lori S C Kreisman, Brian A Cobb
While Toll-like receptors (TLRs) represent one of the best characterized innate immune pathways, evidence suggests that TLRs are not restricted to innate leukocytes and some epithelial cells, but are also expressed in T cells. Specifically, published evidence focusing on FoxP3+ regulatory T cells demonstrate that they express functional TLR2, which is already known among the TLR family for its association with immune suppression; however, little is known about the relationship between T cell-intrinsic TLR2 binding and cytokine production, T cell differentiation, or T cell receptor (TCR) stimulation...
2017: PloS One
https://www.readbyqxmd.com/read/28742815/il33-mediated-ilc2-activation-and-neutrophil-il5-production-in-the-lung-response-after-severe-trauma-a-reverse-translation-study-from-a-human-cohort-to-a-mouse-trauma-model
#2
Jing Xu, Jesse Guardado, Rosemary Hoffman, Hui Xu, Rami Namas, Yoram Vodovotz, Li Xu, Mostafa Ramadan, Joshua Brown, Heth R Turnquist, Timothy R Billiar
BACKGROUND: The immunosuppression and immune dysregulation that follows severe injury includes type 2 immune responses manifested by elevations in interleukin (IL) 4, IL5, and IL13 early after injury. We hypothesized that IL33, an alarmin released early after tissue injury and a known regulator of type 2 immunity, contributes to the early type 2 immune responses after systemic injury. METHODS AND FINDINGS: Blunt trauma patients admitted to the trauma intensive care unit of a level I trauma center were enrolled in an observational study that included frequent blood sampling...
July 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28742217/the-inflammatory-cytokine-interferon-gamma-inhibits-sortilin-1-expression-in-hepatocytes-via-the-jak-stat-pathway
#3
John Pirault, Konstantinos A Polyzos, Marcelo H Petri, Daniel Fj Ketelhuth, Magnus Bäck, Göran K Hansson
Sortilin-1, a receptor of the VPS10p family, has been associated with cardiovascular disease in genome-wide association studies. It is implicated in lipoprotein metabolism, secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) and secretion of inflammatory cytokines. However, its own regulation remains unclear. Chronic inflammation is a hallmark of atherosclerosis and absence of regulatory T (Treg) cells is associated with reduced protein expression of sortilin-1 in the liver. Therefore, we postulated that mediator(s) of inflammation known to be downregulated by regulatory T cells may modulate sortilin-1 expression...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28742189/novel-endogenous-negative-modulators-of-platelet-function-as-potential-anti-thrombotic-targets
#4
Y-J Li, H-X Zhu, D Zhang, H-C Li, P Ma, L-Y Huang
Platelets are megakaryocyte-derived nuclear-free fragments that participate in cardiovascular diseases including acute myocardial infarction, ischemic stroke, hypertension, and atherosclerosis. At the endothelium damage site, platelets interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor γ-chain (GPVI/FcRγ), G protein-coupled receptor/phospholipase Cγ(β) (GPCR/PLCγ(β)), Rho/RhoK and integrin. The activation of these signaling pathways triggers intracellular calcium increase and causes platelet adhesion, aggregation, granule release and finally thrombus formation...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28741728/ebi2-contributes-to-the-induction-of-thymic-central-tolerance-in-mice-by-promoting-rapid-motility-of-medullary-thymocytes
#5
Sanghee Ki, Hiran M Thyagarajan, Zicheng Hu, Jessica N Lancaster, Lauren I R Ehrlich
Maturing thymocytes enter the thymic medulla, where they encounter numerous self-antigens presented by antigen presenting cells (APCs). Those thymocytes that are strongly self-reactive undergo either negative selection or diversion into the regulatory T cell lineage. Although the majority of the proteome is expressed in the medulla, many self-antigens are expressed by only a minor fraction of medullary APCs; thus, thymocytes must efficiently enter the medulla and scan APCs to ensure central tolerance. Chemokine receptors promote lymphocyte migration, organization within tissues, and interactions with APCs in lymphoid organs...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28741409/foxp3-expression-in-lymph-node-metastases-in-patients-with-head-and-neck-cancer
#6
Mehtap Boduc, Marion Roessler, Robert Mandic, Christoph Netzer, Christian Güldner, Ute Walliczek-Dworschak, Boris A Stuck, Magis Mandapathil
INTRODUCTION: The prevalence and activity of regulatory T cells in patients with cancer correlates with poor prognosis. These cells are characterized by their expression of Forkhead box protein-3 (Foxp3). Squamous cell carcinoma is the most prevalent type of cancer in the head and neck region with overall poor survival rates, also due to early spread of metastatic cells. MATERIAL AND METHODS: Primary tumor specimens as well as lymph node specimens harvested during neck dissection of 65 patients with a diagnosis of HNSCC were subjected to immunohistochemical and H-score analysis of Foxp3 expression...
July 25, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28740491/nod-like-receptor-p3-inflammasome-controls-protective-th1-th17-immunity-against-pulmonary-paracoccidioidomycosis
#7
Claudia Feriotti, Eliseu Frank de Araújo, Flavio Vieira Loures, Tania Alves da Costa, Nayane Alves de Lima Galdino, Dario Simões Zamboni, Vera Lucia Garcia Calich
The NOD-like receptor P3 (NLRP3) inflammasome is an intracellular multimeric complex that triggers the activation of inflammatory caspases and the maturation of IL-1β and IL-18, important cytokines for the innate immune response against pathogens. The functional NLRP3 inflammasome complex consists of NLRP3, the adaptor protein apoptosis-associated speck-like protein, and caspase-1. Various molecular mechanisms were associated with NLRP3 activation including the presence of extracellular ATP, recognized by the cell surface P2X7 receptor (P2X7R)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28739765/relationship-of-th17-treg-cells-and-radiation-pneumonia-in-locally-advanced-esophageal-carcinoma
#8
Yan Wang, Gang Xu, Jie Wang, Xin-Hua Li, Ping Sun, Wei Zhang, Jun-Xia Li, Chao-Yang Wu
BACKGROUND/AIM: Radiation pneumonia is a main side-effect that has limited the clinical usage of radiotherapy in locally advanced esophageal carcinoma. T helper cells 17 (Th 17) and T regulatory cells (Tregs) play an important role in inflammatory diseases. The balance between Treg and Th17 cells is a key factor in the progression of many inflammatory and autoimmune diseases. Whether Tregs and Th17 cells are predictive factors of radiation pneumonia has not yet been reported. In this study, we investigated the relationships of Treg/Th17 cells and radiation pneumonia in patients with locally advanced esophageal cancer who received radiotherapy...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28738754/pralatrexate-a-comprehensive-update-on-pharmacology-clinical-activity-and-strategies-to-optimize-use
#9
Owen A O'Connor, Jennifer Amengual, Donald Colbourn, Changchun Deng, Ahmed Sawas
It has been nearly 8 years since pralatrexate became the first drug approved by the U.S. Food and Drug Administration for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL). Like most drugs approved for a particular clinical indication, as much or more is learned once it enters mainstream use as in the years leading up to regulatory approval. Over the past several years, many diverse lines of research have shed new insight into both the agent, and the diseases it treats. In this review, we will bring the reader up to date on the many new aspects related to pralatrexate's pharmacology, activity across the panoply of T-cell lymphoproliferative malignancies, as well as some new and emerging guidelines that are likely to improve its safety profile...
November 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28738016/eomesodermin-promotes-the-development-of-type-1-regulatory-t-tr1-cells
#10
Ping Zhang, Jason S Lee, Kate H Gartlan, Iona S Schuster, Iain Comerford, Antiopi Varelias, Md Ashik Ullah, Slavica Vuckovic, Motoko Koyama, Rachel D Kuns, Kelly R Locke, Kirrilee J Beckett, Stuart D Olver, Luke D Samson, Marcela Montes de Oca, Fabian de Labastida Rivera, Andrew D Clouston, Gabrielle T Belz, Bruce R Blazar, Kelli P MacDonald, Shaun R McColl, Ranjeny Thomas, Christian R Engwerda, Mariapia A Degli-Esposti, Axel Kallies, Siok-Keen Tey, Geoffrey R Hill
Type 1 regulatory T (TR1) cells are Foxp3(-) interleukin-10 (IL-10)-producing CD4(+) T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages...
April 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28737722/induction-of-a-regulatory-phenotype-in-cd3-cd4-hla-dr-t-cells-after-allogeneic-mixed-lymphocyte-culture-indications-of-both-contact-dependent-and-independent-activation
#11
Anne Louise Schacht Revenfeld, Rikke Bæk, Malene Møller Jørgensen, Kim Varming, Allan Stensballe
Although the observation of major histocompatibility complex II (MHCII) receptors on T cells is longstanding, the explanation for this occurrence remains enigmatic. Reports of an inducible, endogenous expression exist, as do studies demonstrating a protein acquisition from other cells by mechanisms including vesicle transfer. Irrespective of origin, the presence of the human MHCII isotype, human leukocyte antigen DR (HLA-DR), potentially identifies a regulatory T cell population. Using an allogeneic mixed lymphocyte culture (MLC) to induce an antigen-specific immune response, the role of antigen-presenting cells (APCs) for the presence of HLA-DR on cluster of differentiation 3(CD3)+ CD4+ T cells was evaluated...
July 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28736999/regulatory-t-cell-subsets-in-peripheral-blood-of-celiac-disease-patients-and-tlr2-expression-correlation-with-oxidative-stress
#12
Sanjay Kumar, Sadhna Lal, Archana Bhatnagar
The study was carried out to study expression of Toll like receptors 2 (TLR2), natural/inducible Treg and Interferon-γ alongside oxidative stress and understand their significance in pediatric samples. Influence of oxidative stress on Celiac Disease was analysed by evaluating lipid peroxidation, reduced glutathione, Glutathione peroxidase, etc. A comparison was performed among CD patients, CD patients on gluten free diet (GFD), and healthy controls. Peripheral nTregs exhibited a similar pattern of reduced numbers in CD and GFD cases when compared to healthy controls...
July 24, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28736945/tim-1-b-cells-suppress-t-cell-interferon-gamma-production-and-promote-foxp3-expression-but-have-impaired-regulatory-function-in-coronary-artery-disease
#13
Xiao-Long Gu, Huan He, Lin Lin, Guo-Xin Luo, Yan-Fei Wen, Ding-Cheng Xiang, Jian Qiu
Atherosclerosis and its associated coronary artery disease (CAD) represent another chronic low-grade inflammatory disorder. Regulatory B cells (Bregs) possess essential functions in maintaining peripheral tolerance and inhibiting pathogenic inflammation through IL-10. Here, we investigated one subset of Bregs, Tim-1(+) B cell, and its role in atherosclerosis and CAD patients. In healthy individuals, IL-10-producing B cells were predominantly found in the Tim-1(+) B cells. Upon stimulation of the B cell receptor (BCR) and Toll-like receptor 9 (TLR-9) by anti-BCR antibodies and CpG, respectively, the Tim-1(+) B cells could further upregulate IL-10 expression...
July 24, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28736941/in-vivo-neutralization-of-%C3%AE-4-and-%C3%AE-7-integrins-inhibits-eosinophil-trafficking-and-prevents-lung-injury-during-tropical-pulmonary-eosinophilia-in-mice
#14
Pankaj Sharma, Aditi Sharma, Mrigank Srivastava
Integrins regulate leukocyte trafficking during homeostasis and inflammatory conditions. However, the role of α4 and β7 integrins in guiding eosinophil transmigration into the lungs during filarial manifestation of Tropical Pulmonary Eosinophilia (TPE) has not been explored. In this study, mice exhibiting TPE manifestations were administered with in vivo neutralizing antibodies against integrins α4 and β7 or their combination and immuno-pathological parameters were evaluated. Results show an intact lung barrier, significantly lower lung inflammation and reduced eosinophil counts in the Bronchoalveolar lavage fluid and lungs of mice receiving anti-α4(+) β7 treatment...
July 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28736829/clonal-analysis-of-regulatory-t-cell-defect-in-patients-with-autoimmune-polyendocrine-syndrome-type-1-suggests-intrathymic-impairment
#15
Tuisku-Tuulia Koivula, Sini M Laakso, Heikki J Niemi, Eliisa Kekäläinen, Pia Laine, Lars Paulin, Petri Auvinen, T Petteri Arstila
Mutations in the Autoimmune Regulator (AIRE) gene disrupt thymic T cell development and negative selection, leading to the recessively inherited polyendocrine autoimmune disease APS-1 (autoimmune polyendocrine syndrome type 1). The patients also have a functional defect in the FOXP3(+) regulatory T cell population, but its origin is unclear. Here we have used T cell receptor sequencing to analyze the clonal relationship of major CD4(+) T cell subsets in 3 patients and 3 healthy controls. The naive regulatory T cells showed little overlap with helper T cell subsets, supporting divergence in the thymus...
July 22, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28736551/differential-phenotypes-of-myeloid-derived-suppressor-and-t-regulatory-cells-and-cytokine-levels-in-amnestic-mild-cognitive-impairment-subjects-compared-to-mild-alzheimer-diseased-patients
#16
Aurélie Le Page, Hugo Garneau, Gilles Dupuis, Eric H Frost, Anis Larbi, Jacek M Witkowski, Graham Pawelec, Tamàs Fülöp
Alzheimer disease (AD) is the most prevalent form of dementia although the underlying cause(s) remains unknown at this time. However, neuroinflammation is believed to play an important role and suspected contributing immune parameters can be revealed in studies comparing patients at the stage of amnestic mild cognitive impairment (aMCI) to healthy age-matched individuals. A network of immune regulatory cells including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) maintains immune homeostasis but there are very few data on the role of these cells in AD...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28736524/immune-and-metabolic-regulation-mechanism-of-dangguiliuhuang-decoction-against-insulin-resistance-and-hepatic-steatosis
#17
Hui Cao, Lingling Tuo, Yali Tuo, Ziyun Xia, Rong Fu, Yang Liu, Yihong Quan, Jue Liu, Zhihong Yu, Ming Xiang
Dangguiliuhuang decoction (DGLHD) is a traditional Chinese medicine (TCM) formula, which mainly consists of angelica, radix rehmanniae, radix rehmanniae praeparata, scutellaria baicalensis, coptis chinensis, astragalus membranaceus, and golden cypress, and used for the treatment of diabetes and some autoimmune diseases. In this study, we explored the potential mechanism of DGLHD against insulin resistance and fatty liver in vivo and in vitro. Our data revealed that DGLHD normalized glucose and insulin level, increased the expression of adiponectin, diminished fat accumulation and lipogenesis, and promoted glucose uptake...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28736431/combined-blockade-of-t-cell-immunoglobulin-and-mucin-domain-3-and-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-results-in-durable-therapeutic-efficacy-in-mice-with-intracranial-gliomas
#18
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28736280/the-serine-threonine-protein-phosphatase-2a-controls-autoimmunity
#19
Amir Sharabi, Isaac R Kasper, George C Tsokos
Protein phosphatase 2A (PP2A) is the first Ser/Thr phosphatase recognized to contribute to human and murine lupus immunopathology. PP2A expression in SLE is controlled both epigenetically and genetically, and it is increased in patients with SLE, which contributes to decreased IL-2 production, decreased CD3ζ and increased FcRγ expression on the surface of T cells, increased CREMα expression, hypomethylation of genes associated with SLE pathogenesis, and increased IL-17 production. B regulatory subunit of PP2A regulates IL-2 deprivation-induced T cell death and is decreased in SLE patients...
July 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28736203/oral-administration-of-visceral-adipose-tissue-antigens-ameliorates-metabolic-disorders-in-mice-and-elevates-visceral-adipose-tissue-resident-cd4-cd25-foxp3-regulatory-t-cells
#20
Xiangyu Chen, Dali Zhang, Xiaoling Chen, Gang Meng, Qian Zheng, Wenli Mai, Yuzhang Wu, Lilin Ye, Li Wang
Obesity and type 2 diabetes are linked with chronic, low-grade inflammation in visceral adipose tissue (VAT). A unique population of VAT-resident CD4(+)Foxp3(+) Tregs plays a crucial role in regulating VAT inflammation and metabolic homeostasis. VAT-resident Tregs display a highly restricted TCR repertoire, suggesting they recognize certain autoantigen(s) in VAT. A dramatic reduction of VAT-resident Tregs has been shown to closely correlate with obesity-related VAT chronic inflammation and metabolic disorders...
July 20, 2017: Vaccine
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