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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
#1
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
#2
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 integration of GWAS and eQTL data from the TwinsUK microarray and RNA-Seq cohort in lymphoblastoid cell lines...
January 5, 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
#3
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...
December 24, 2016: Human Immunology
https://www.readbyqxmd.com/read/27994068/resetting-microbiota-by-lactobacillus-reuteri-inhibits-t-reg-deficiency-induced-autoimmunity-via-adenosine-a2a-receptors
#4
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
#5
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...
October 21, 2016: Human Antibodies
https://www.readbyqxmd.com/read/27765276/the-role-of-toll-like-receptor-9-in-gynecologic-cancer
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27523950/cytokine-gene-expression-in-aborting-and-non-aborting-dams-and-in-their-foetuses-after-experimental-infection-with-neospora-caninum-at-110-days-of-gestation
#12
S Almeria, B Serrano-Pérez, L Darwich, R Mur-Novales, I Garcia-Ispierto, O Cabezón, F López-Gatius
Neospora caninum is a major cause of abortion in cattle. However, it is not known why not all infected animals abort. In this study, Th1 (IFN-γ), Th2 (IL4) and T reg (IL-10) cytokine gene expression was examined by real time PCR using the TaqMan approach in all of these dams and their foetuses after experimental infection with the isolate Nc-Spain7 at 110 days of pregnancy and euthanasia 6 weeks after infection. In prior published work, foetal death was observed in three of six infected dams and transplacental infection in all the 6 infected foetuses...
August 30, 2016: Veterinary Parasitology
https://www.readbyqxmd.com/read/27508639/-op-2d-04-perivascular-t-regulatory-cells-and-endothelial-dysfunction-in-human-atherosclerosis
#13
K Urbanski, G Filip, M Filip, D Ludew, P Szczepaniak, R Nosalski, A Sagan, T Mikolajczyk, B Kapelak, T J Guzik
OBJECTIVE: Atherosclerosis is an inflammatory disease associated with an imbalance between pro- and anti-inflammatory mechanisms. While ample evidence is available in animal models, less is known about links between local vascular inflammation in human disease. T regulatory cells (Treg) have been implicated in atherosclerosis in mice but links with human vascular inflammation are poorly understood. Accordingly, we aimed to investigate the relationship between T regs in peripheral blood and locally in perivascular adipose tissue (pVAT) with endothelial function as a key mechanism in pathogenesis of vascular disease...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27477596/immunophenotyping-of-t-cells-in-the-peripheral-circulation-in-psoriasis
#14
M Priyadarssini, D Divya Priya, S Indhumathi, Medha Rajappa, Laxmisha Chandrashekar, D M Thappa
BACKGROUND: Psoriasis is a T-helper (Th)-1/Th17-mediated chronic inflammatory disease. Cytokine mediated interaction between T lymphocytes and keratinocytes lead to keratinocyte hyper-proliferation, which leads to further inflammation in the psoriatic plaques. There is an increased population of T-helper cells in the skin lesions as well as in the peripheral circulation in psoriasis. However, the relative percentage of each T-cell phenotype in the disease pathogenesis is understudied...
October 2016: British Journal of Biomedical Science
https://www.readbyqxmd.com/read/27441095/mycobacterium-tuberculosis-induces-expansion-of-foxp3-positive-cd4-t-cells-with-a-regulatory-profile-in-tuberculin-non-sensitized-healthy-subjects-implications-for-effective-immunization-against-tb
#15
Christina S Hirsch, Roxana Rojas, Mianda Wu, Zahra Toossi
OBJECTIVE: Infection by MTB or exposure to MTB constituents is associated with intense microbial stimulation of the immune system, through both antigenic and TLR components, and induction of a milieu that is rich in pro-inflammatory/anti-inflammatory cytokines. Here, we addressed the basis of induced regulatory T-cell (iT-reg) expansion in response to MTB stimulation, in the absence of prior T cell antigen responsiveness. METHODS: PBMC from HIV-1 un-infected TST negative and TST positive control subjects were stimulated by virulent MTB H37Rv lysate (L), a French press preparation of MTB that includes all bacterial components...
June 2016: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/27437104/b-cell-regulation-of-the-anti-tumor-response-and-role-in-carcinogenesis
#16
REVIEW
Marc Schwartz, Yu Zhang, Joseph D Rosenblatt
The balance between immune effector cells such as T cells and natural killer cells, and immunosuppressive Treg cells, dendritic, myeloid and monocytic sub-populations in the tumor microenvironment acts to calibrate the immune response to malignant cells. Accumulating evidence is pointing to a role for B cells in modulating the immune response to both solid tumors and hematologic cancer. Evidence from murine autoimmune models has defined B regulatory cell (Breg) subsets that express cytokines such as IL-10, TGF-β, and/or express immune regulatory ligands such as PD-L1, which can suppress T cell and/or natural killer cell responses...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27404095/recombinant-hla-g-as-tolerogenic-immunomodulant-in-experimental-small-bowel-transplantation
#17
Martin W von Websky, Koji Kitamura, Isis Ludwig-Portugall, Christian Kurts, Maximilian von Laffert, Joel LeMaoult, Edgardo D Carosella, Kareem Abu-Elmagd, Joerg C Kalff, Nico Schäfer
The non-classical MHC I paralogue HLA-G is expressed by cytotrophoblast cells and implicated with fetomaternal tolerance by downregulating the maternal adaptive and innate immune response against the fetus. HLA-G expression correlates with favorable graft outcome in humans and recently promising immunosuppressive effects of therapeutic HLA-G in experimental transplantation (skin allograft acceptance) were shown. Consequently, we examined this novel therapeutic approach in solid organ transplantation. In this study, therapeutic recombinant HLA-G5 was evaluated for the first time in a solid organ model of acute rejection (ACR) after orthotopic intestinal transplantation (ITX)...
2016: PloS One
https://www.readbyqxmd.com/read/27393133/physiologic-doses-of-bilirubin-contribute-to-tolerance-of-islet-transplants-by-suppressing-the-innate-immune-response
#18
Christopher A Adin, Zachary C VanGundy, Tracey L Papenfuss, Feng Xu, Mostafa Ghanem, Jonathan Lakey, Gregg A Hadley
Bilirubin has been recognized as a powerful cytoprotectant when used at physiologic doses and was recently shown to have immunomodulatory effects in islet allograft transplantation, conveying donor specific tolerance in a murine model. We hypothesized that bilirubin, an antioxidant, acts to suppress the innate immune response to islet allografts through two mechanisms: 1) by suppressing graft release of damage associated molecular patterns (DAMPs) and inflammatory cytokines, and 2) by producing a tolerogenic phenotype in antigen presenting cells...
July 7, 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27377588/cd6-modulates-thymocyte-selection-and-peripheral-t-cell-homeostasis
#19
Marc Orta-Mascaró, Marta Consuegra-Fernández, Esther Carreras, Romain Roncagalli, Amado Carreras-Sureda, Pilar Alvarez, Laura Girard, Inês Simões, Mario Martínez-Florensa, Fernando Aranda, Ramón Merino, Vanesa-Gabriela Martínez, Rubén Vicente, Jesús Merino, Adelaida Sarukhan, Marie Malissen, Bernard Malissen, Francisco Lozano
The CD6 glycoprotein is a lymphocyte surface receptor putatively involved in T cell development and activation. CD6 facilitates adhesion between T cells and antigen-presenting cells through its interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), and physically associates with the T cell receptor (TCR) at the center of the immunological synapse. However, its precise role during thymocyte development and peripheral T cell immune responses remains to be defined. Here, we analyze the in vivo consequences of CD6 deficiency...
July 25, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27270893/anti-tnf-drives-regulatory-t-cell-expansion-by-paradoxically-promoting-membrane-tnf-tnf-rii-binding-in-rheumatoid-arthritis
#20
Dao Xuan Nguyen, Michael R Ehrenstein
The interplay between inflammatory and regulatory pathways orchestrates an effective immune response that provides protection from pathogens while limiting injury to host tissue. Tumor necrosis factor (TNF) is a pivotal inflammatory cytokine, but there is conflicting evidence as to whether it boosts or inhibits regulatory T cells (T reg cells). In this study, we show that the therapeutic anti-TNF antibody adalimumab, but not the soluble TNF receptor etanercept, paradoxically promoted the interaction between monocytes and T reg cells isolated from patients with rheumatoid arthritis (RA)...
June 27, 2016: Journal of Experimental Medicine
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