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https://www.readbyqxmd.com/read/28362433/il-2-prevents-deletion-of-developing-t-regulatory-cells-in-the-thymus
#1
Daniel Y Hu, Rushika C Wirasinha, Christopher C Goodnow, Stephen R Daley
In the thymus, strongly self-reactive T cells may undergo apoptotic deletion or differentiate into Foxp3+ T-regulatory (T-reg) cells. Mechanisms that partition T cells into these two fates are unclear. Here, we show that IL-2 signalling is required to prevent deletion of CD4+ CD8- CCR7+ Helios+ thymocytes poised to upregulate Foxp3. The deletion prevented by IL-2 signalling is Foxp3 independent and occurs later in thymocyte development than the deletion that is prevented by Card11 signalling. Our results distinguish two bottlenecks at which strongly self-reactive thymocytes undergo deletion or progress to the next stage of T-reg differentiation; Card11 regulates the first bottleneck and IL-2 regulates the second...
March 31, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28332200/immunoregulation-of-inflammatory-and-inhibitory-cytokines-by-vitamin-d3-in-patients-with-inflammatory-bowel-diseases-ibd
#2
REVIEW
Hussaini Mohammed Alhassan, Abbas Mirshafiey, Homayoun Vahedi, Gholamreza Hemmasi, Ateke Moussavi Nasl Khameneh, Karim Parastouei, Ali Akbar Saboor-Yaraghi
Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract, caused by an aberrant and exaggerated immunological response in the gut. Supplementation of Vitamin D3 in IBD patients exerts both direct and indirect regulatory roles on the naïve T-cells, thereby maintaining a balance between inflammatory and inhibitory cytokines. The direct actions of Vitamin D3 on naïve T-cells result in the proliferation of more regulatory T-cells and inhibitory cytokines such as IL-4, IL-10, and IL-5...
March 22, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28316421/immunophenotyping-of-blood-mononuclear-cells-from-p-berghei-nk-65-infected-and-immunized-balb-c-mice
#3
Vineet Kumar, Aruna Rakha, Ruchika Saroa, Upma Bagai
The present study demonstrates the alterations in the frequencies of helper, cytotoxic and suppressor T cells in blood of P. berghei infected and TPA immunized rodent host towards the induction of protective immune response. Statistically significant (p < 0.005) number of CD4(+) T cells was recorded on D9 [Post Challenge (PC)] meanwhile CD4(+) Treg cells were found to be declined in immunized mice as compared to infected. This increase in frequencies of T helper cells points towards the stimulation of strong Th2 immune response in immunized mice...
March 2017: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/28293742/the-accumulation-of-regulatory-t-cells-in-the-hepatic-hilar-lymph-nodes-in-biliary-atresia
#4
Naoya Sakamoto, Toshihiro Muraji, Haruo Ohtani, Kouji Masumoto
PURPOSE: A proposed etiopathogenesis of biliary atresia (BA) involves T-cell-mediated inflammatory bile duct damage and progressive hepatic fibrosis. Pediatric surgeons often observe swelling of the hepatic hilar lymph nodes during the Kasai procedure. Given the importance of regulatory mechanisms in immune responses, the present study was designed to analyze the quantitative changes of regulatory T cells (T reg cells) in the hepatic hilar lymph nodes (hepatic hilar LNs) and peripheral blood (PB) in BA...
March 14, 2017: Surgery Today
https://www.readbyqxmd.com/read/28228153/assessment-of-axillary-temperature-for-the-evaluation-of-normal-body-temperature-of-healthy-young-adults-at-rest-in-a-thermoneutral-environment
#5
Shuri Marui, Ayaka Misawa, Yuki Tanaka, Kei Nagashima
BACKGROUND: The aims of this study were to (1) evaluate whether recently introduced methods of measuring axillary temperature are reliable, (2) examine if individuals know their baseline body temperature based on an actual measurement, and (3) assess the factors affecting axillary temperature and reevaluate the meaning of the axillary temperature. METHODS: Subjects were healthy young men and women (n = 76 and n = 65, respectively). Three measurements were obtained: (1) axillary temperature using a digital thermometer in a predictive mode requiring 10 s (T ax-10 s), (2) axillary temperature using a digital thermometer in a standard mode requiring 10 min (T ax-10 min), and (3) tympanic membrane temperature continuously measured by infrared thermometry (T ty)...
February 22, 2017: Journal of Physiological Anthropology
https://www.readbyqxmd.com/read/28130403/suppression-of-lethal-autoimmunity-by-regulatory-t-cells-with-a-single-tcr-specificity
#6
Andrew G Levine, Saskia Hemmers, Antonio P Baptista, Michail Schizas, Mehlika B Faire, Bruno Moltedo, Catherine Konopacki, Marc Schmidt-Supprian, Ronald N Germain, Piper M Treuting, Alexander Y Rudensky
The regulatory T cell (T reg cell) T cell receptor (TCR) repertoire is highly diverse and skewed toward recognition of self-antigens. TCR expression by T reg cells is continuously required for maintenance of immune tolerance and for a major part of their characteristic gene expression signature; however, it remains unknown to what degree diverse TCR-mediated interactions with cognate self-antigens are required for these processes. In this study, by experimentally switching the T reg cell TCR repertoire to a single T reg cell TCR, we demonstrate that T reg cell function and gene expression can be partially uncoupled from TCR diversity...
March 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28125674/characterisation-of-immune-and-neuroinflammatory-changes-associated-with-chemotherapy-induced-peripheral-neuropathy
#7
Preet G S Makker, Samuel S Duffy, Justin G Lees, Chamini J Perera, Ryan S Tonkin, Oleg Butovsky, Susanna B Park, David Goldstein, Gila Moalem-Taylor
Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain is a debilitating adverse effect of cancer treatment. Current understanding of the mechanisms underpinning CIPN is limited and there are no effective treatment strategies. In this study, we treated male C57BL/6J mice with 4 cycles of either Paclitaxel (PTX) or Oxaliplatin (OXA) over a week and tested pain hypersensitivity and changes in peripheral immune responses and neuroinflammation on days 7 and 13 post 1st injection. We found that both PTX and OXA caused significant mechanical allodynia...
2017: PloS One
https://www.readbyqxmd.com/read/28119177/immunoparalysis-clinical-and-immunological-associations-in-sirs-and-severe-sepsis-patients
#8
Panagiotis Papadopoulos, Aikaterini Pistiki, Maria Theodorakopoulou, Theodora Christodoulopoulou, Georgia Damoraki, Dimitris Goukos, Efrossini Briassouli, Ioanna Dimopoulou, Apostolos Armaganidis, Serafim Nanas, George Briassoulis, Sotirios Tsiodras
INTRODUCTION: This study was designed to identify changes in the monocytic membrane marker HLA-DR and heat shock proteins (HSPs) in relation to T-regulatory cells (T-regs) and other immunological marker changes in patients with systemic inflammatory response syndrome (SIRS) or sepsis/septic shock. METHODS: Healthy volunteers, intensive care unit (ICU) patients with SIRS due to head injury and ICU patients with severe sepsis/septic shock were enrolled in the current study...
April 2017: Cytokine
https://www.readbyqxmd.com/read/28114571/effect-of-corneal-nerve-ablation-on-immune-tolerance-induced-by-corneal-allografts-oral-immunization-or-anterior-chamber-injection-of-antigens
#9
Juan Mo, Sudha Neelam, Jessamee Mellon, Joseph R Brown, Jerry Y Niederkorn
Purpose: Severing corneal nerves during corneal transplantation does not affect first corneal transplants, but abolishes immune privilege of subsequent corneal allografts. This abrogation of immune privilege is attributable to the disabling of T regulatory cells (T regs) induced by corneal transplantation. The goal of this study was to determine if severing corneal nerves induces the development of contrasuppressor (CS) cells, which disable T regs that impair other forms of immune tolerance...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28069723/a-novel-murine-gitr-ligand-fusion-protein-induces-antitumor-activity-as-a-monotherapy-which-is-further-enhanced-in-combination-with-an-ox40-agonist
#10
Rebecca Leyland, Amanda Watkins, Kathy Mulgrew, Nicholas Holoweckyj, Lisa Bamber, Natalie J Tigue, Emily Offer, John Andrews, Li Yan, Stefanie Mullins, Michael D Oberst, Jane Coates Ulrichsen, David A Leinster, Kelly A McGlinchey, Lesley Young, Michelle Morrow, Scott A Hammond, Philip R Mallinder, Athula Herath, Ching Ching Leow, Robert W Wilkinson, Ross Stewart
PURPOSE: To generate and characterize a murine GITR ligand fusion protein (mGITRL-FP) designed to maximize valency and the potential to agonize the GITR receptor for cancer immunotherapy. EXPERIMENTAL DESIGN: The EC50 value of the mGITRL-FP was compared to an anti-GITR antibody in an in vitro agonistic cell based reporter assay. We assessed the impact of dose, schedule and Fc isotype on antitumor activity and T-cell modulation in the CT26 tumor model. The activity of the mGITRL-FP was compared to an agonistic murine OX40L-FP targeting OX40, in CT26 and B16F10-Luc2 tumor models...
January 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28062664/mapping-eqtls-with-rna-seq-reveals-novel-susceptibility-genes-non-coding-rnas-and-alternative-splicing-events-in-systemic-lupus-erythematosus
#11
Christopher A Odhams, Andrea Cortini, Lingyan Chen, Amy L Roberts, Ana Viñuela, Alfonso Buil, Kerrin S Small, Emmanouil T Dermitzakis, David L Morris, Timothy J Vyse, Deborah S Cunninghame Graham
Studies attempting to functionally interpret complex-disease susceptibility loci by GWAS and eQTL integration have predominantly employed microarrays to quantify gene-expression. RNA-Seq has the potential to discover a more comprehensive set of eQTLs and illuminate the underlying molecular consequence. We examine the functional outcome of 39 variants associated with Systemic Lupus Erythematosus (SLE) through the integration of GWAS and eQTL data from the TwinsUK microarray and RNA-Seq cohort in lymphoblastoid cell lines...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28027921/t-helper-2-cytokine-regulatory-t-cell-gene-polymorphisms-and-their-relation-with-risk-of-psoriasis-in-a-south-indian-tamil-cohort
#12
Sundar Indhumathi, Medha Rajappa, Laxmisha Chandrashekar, Palghat Hariharan Ananthanarayanan, Devinder Mohan Thappa, Vir Singh Negi
BACKGROUND: Psoriasis is known to be associated with an up-regulation of T-helper (Th)-1 & Th-17 cytokines and a relative down-regulation of Th-2 and T-regulatory (T-reg) cytokines. Certain allelic variants of these cytokine genes may alter Th1/Th17 and Th2/T-reg balance and may be associated with the risk of psoriasis. Hence we aimed to determine the association of IL-4 (rs2243250), IL-10 (rs1800871 and rs1800896) and FOXP3 (rs3761548) gene polymorphisms with risk of psoriasis in South Indian Tamils...
February 2017: Human Immunology
https://www.readbyqxmd.com/read/27994068/resetting-microbiota-by-lactobacillus-reuteri-inhibits-t-reg-deficiency-induced-autoimmunity-via-adenosine-a2a-receptors
#13
Baokun He, Thomas K Hoang, Ting Wang, Michael Ferris, Christopher M Taylor, Xiangjun Tian, Meng Luo, Dat Q Tran, Jain Zhou, Nina Tatevian, Fayong Luo, Jose G Molina, Michael R Blackburn, Thomas H Gomez, Stefan Roos, J Marc Rhoads, Yuying Liu
Regulatory T (T reg) cell deficiency causes lethal, CD4(+) T cell-driven autoimmune diseases. Stem cell transplantation is used to treat these diseases, but this procedure is limited by the availability of a suitable donor. The intestinal microbiota drives host immune homeostasis by regulating the differentiation and expansion of T reg, Th1, and Th2 cells. It is currently unclear if T reg cell deficiency-mediated autoimmune disorders can be treated by targeting the enteric microbiota. Here, we demonstrate that Foxp3(+) T reg cell deficiency results in gut microbial dysbiosis and autoimmunity over the lifespan of scurfy (SF) mouse...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27792007/single-nucleotide-polymorphisms-in-the-foxp3-gene-are-associated-with-increased-risk-of-relapsing-remitting-multiple-sclerosis
#14
Mohammad Mahdi Eftekharian, Arezou Sayad, Mir Davood Omrani, Masoud Sabouri Ghannad, Rezvan Noroozi, Mehrdokht Mazdeh, Reza Mirfakhraie, Abolfazl Movafagh, Ghodratollah Roshanaei, Tahereh Azimi, Hidetoshi Inoko, Mohammad Taheri
BACKGROUND: Although Multiple Sclerosis (MS) is an autoimmune multifactorial disease with unknown etiology, various genetic and environmental factors are known to contribute to the pathogenesis of the disease. OBJECTIVE: Recent studies have confirmed that the suppressive function of regulatory T cells (T (reg)) is impaired in MS patients and that the FOXP3 gene is a crucial transcription factor in the regulation of CD4+CD25+FOXP3+ Treg cells. Polymorphisms in the promoter region of the FOXP3 gene may alter the gene expression level and, therefore, contribute to the disease susceptibility...
2016: Human Antibodies
https://www.readbyqxmd.com/read/27765276/the-role-of-toll-like-receptor-9-in-gynecologic-cancer
#15
E Fehri, E Ennaifer, R Bel Haj Rhouma, L Guizani-Tabbane, I Guizani, S Boubaker
Toll-like receptor 9 (TLR9) plays a major role in the fight against DNA viruses infections. Despite its antitumor properties, inappropriate activation of TLR9 during chronic inflammation may cause the activation of transcription factors inducing pro-cancerous activities. Thus, the relationship between TLR9 and cancer remains highly confrontational especially in gynecological cancers and cervical cancer induced by viruses. In this review, we focus on the beneficial and detrimental role of TLR9 in gynecological carcinogenesis...
July 2016: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/27715088/how-isotropic-is-the-universe
#16
Daniela Saadeh, Stephen M Feeney, Andrew Pontzen, Hiranya V Peiris, Jason D McEwen
A fundamental assumption in the standard model of cosmology is that the Universe is isotropic on large scales. Breaking this assumption leads to a set of solutions to Einstein's field equations, known as Bianchi cosmologies, only a subset of which have ever been tested against data. For the first time, we consider all degrees of freedom in these solutions to conduct a general test of isotropy using cosmic microwave background temperature and polarization data from Planck. For the vector mode (associated with vorticity), we obtain a limit on the anisotropic expansion of (σ_{V}/H)_{0}<4...
September 23, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/27678500/applications-and-mechanisms-of-immunotherapy-in-allergic-rhinitis-and-asthma
#17
Jasper H Kappen, Stephen R Durham, Hans In 't Veen, Mohamed H Shamji
Clinical and immunologic tolerance are hallmarks of successful allergen immunotherapy (AIT). Clinical benefits such as reduced symptoms, pharmacotherapy intake and improvement of quality of life persist following cessation of treatment. Successful AIT is associated with suppression of allergic inflammatory cells such as mast cells, eosinophils and basophils in target organs. Furthermore, AIT down-regulates type 2 innate lymphoid cells and allergen-specific type 2 T-helper (Th2) cells. The immunologic tolerant state following AIT is associated with the induction of distinct phenotypes of regulatory T-cells (T-regs) including interleukin (IL)-10-, IL-35- and transforming growth factor (TGF)-β- producing T-regs and FoxP3(+) T-regs...
January 2017: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/27676155/coexistence-of-th1-th2-and-th17-treg-imbalances-in-patients-with-post-traumatic-sepsis
#18
Dublu Lal Gupta, Sanjeev Bhoi, Teena Mohan, Sagar Galwnkar, D N Rao
INTRODUCTION: Multiple organ dysfunction syndrome (MODS) developed due to the insult of trauma is a leading cause of death. The high mortality rate in these patients with and without sepsis has been reported up to 50%, throughout the world and thus required an urgent insight to overcome this problem. OBJECTIVE: The aim of this study is to examine the differential changes in subsets of T cells, imbalance in cytokine profile, immune-paralysis (T cell anergy) in Trauma hemorrhagic shock (THS) and post traumatic sepsis patients...
December 2016: Cytokine
https://www.readbyqxmd.com/read/27554813/probiotic-supplementation-has-little-effect-on-peripheral-blood-regulatory-t%C3%A2-cells
#19
Nicholas P West, Peggy L Horn, David B Pyne, Hilary S Warren, Suzanne Asad, Amanda J Cox, Sampo J Lahtinen, Markus J Lehtinen, Peter A Fricker, Allan W Cripps, Barbara Fazekas de St Groth
No abstract text is available yet for this article.
December 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27526711/exogenous-tnfr2-activation-protects-from-acute-gvhd-via-host-t-reg-cell-expansion
#20
Martin Chopra, Marlene Biehl, Tim Steinfatt, Andreas Brandl, Juliane Kums, Jorge Amich, Martin Vaeth, Janina Kuen, Rafaela Holtappels, Jürgen Podlech, Anja Mottok, Sabrina Kraus, Ana-Laura Jordán-Garrote, Carina A Bäuerlein, Christian Brede, Eliana Ribechini, Andrea Fick, Axel Seher, Johannes Polz, Katja J Ottmüller, Jeanette Baker, Hidekazu Nishikii, Miriam Ritz, Katharina Mattenheimer, Stefanie Schwinn, Thorsten Winter, Viktoria Schäfer, Sven Krappmann, Hermann Einsele, Thomas D Müller, Matthias J Reddehase, Manfred B Lutz, Daniela N Männel, Friederike Berberich-Siebelt, Harald Wajant, Andreas Beilhack
Donor CD4(+)Foxp3(+) regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT [allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology...
August 22, 2016: Journal of Experimental Medicine
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