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Immune tolerance

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https://www.readbyqxmd.com/read/28813417/cmtm6-maintains-the-expression-of-pd-l1-and-regulates-anti-tumour-immunity
#1
Marian L Burr, Christina E Sparbier, Yih-Chih Chan, James C Williamson, Katherine Woods, Paul A Beavis, Enid Y N Lam, Melissa A Henderson, Charles C Bell, Sabine Stolzenburg, Omer Gilan, Stuart Bloor, Tahereh Noori, David W Morgens, Michael C Bassik, Paul J Neeson, Andreas Behren, Phillip K Darcy, Sarah-Jane Dawson, Ilia Voskoboinik, Joseph A Trapani, Jonathan Cebon, Paul J Lehner, Mark A Dawson
Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR-Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28812775/polymorphic-light-eruption-and-il-1-family-members-any-difference-with-allergic-contact-dermatitis
#2
S Lembo, G Caiazzo, N Balato, G Monfrecola, V Patra, P Wolf, A Balato
Polymorphic light eruption (PLE) is described as a delayed-type hypersensitivity reaction (DTHR) toward a de novo light-induced antigen, yet to be identified. In effect, the inflammatory pathways of PLE and allergic contact dermatitis (ACD) share common patterns in terms of the mediators involved from the innate and adaptive immune system participating in the DTHR. As we have previously highlighted the role of interleukin (IL)-1 family members in ACD, we hypothesised that the same mediators could have similar functions in PLE...
August 16, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28812766/modulatory-effects-of-arginine-glutamine-and-branched-chain-amino-acids-on-heat-shock-proteins-immunity-and-antioxidant-response-in-exercised-rats
#3
Carolina Soares Moura, Pablo Christiano Barboza Lollo, Priscila Neder Morato, Eder Muller Risso, Jaime Amaya-Farfan
Heat shock proteins (HSPs) are endogenous proteins whose function is to maintain the cell's tolerance to insult, and glutamine supplementation is known to increase HSP expression during intense exercise. Since few studies have addressed the possibility that supplementation with other amino acids could have similar effects to that of glutamine, our objective was to evaluate the effects of leucine, valine, isoleucine and arginine as potential stimulators of HSPs 25, 60, 70 and 90 in rats subjected to acute exercise as a stressing factor...
August 16, 2017: Food & Function
https://www.readbyqxmd.com/read/28812547/lung-epithelial-cells-therapeutically-inducible-effectors-of-antimicrobial-defense
#4
REVIEW
M M Leiva-Juárez, J K Kolls, S E Evans
Lung epithelial cells are increasingly recognized to be active effectors of microbial defense, contributing to both innate and adaptive immune function in the lower respiratory tract. As immune sentinels, lung epithelial cells detect diverse pathogens through an ample repertoire of membrane-bound, endosomal, and cytosolic pattern-recognition receptors (PRRs). The highly plastic epithelial barrier responds to detected threats via modulation of paracellular flux, intercellular communications, mucin production, and periciliary fluid composition...
August 16, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28811965/adjuvant-immunotherapy-with-autologous-dendritic-cells-for-hepatocellular-carcinoma-randomized-phase-ii-study
#5
Jeong-Hoon Lee, Won Young Tak, Yoon Lee, Min-Kyu Heo, Jae-Sung Song, Hak-Yeop Kim, Soo Young Park, Si Hyun Bae, Joon Hyeok Lee, Jeong Heo, Ki-Hwan Kim, Yong-Soo Bae, Yoon Jun Kim
Our previous phase I/IIA study showed that autologous dendritic cells (DCs) pulsed with tumor-associated antigens are well tolerated in patients with hepatocellular carcinoma (HCC). In this randomized, multicenter, open-label, phase II trial, we investigated the efficacy and safety of this DC-based adjuvant immunotherapy with 156 patients, who treated for HCC with no evidence of residual tumor after standard treatment modalities. Patients were randomly assigned to immunotherapy (n = 77; injection of 3 × 10(7) DC cells, six times over 14 weeks) or control (n = 79; no treatment)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811651/inkt-cells-prevent-obesity-induced-hepatic-steatosis-in-mice-in-a-c-c-chemokine-receptor-7-dependent-manner
#6
H M Kim, R Lee, E S Lee, M H Kwon, J H Huh, B-E Kwon, E-K Park, S-Y Chang, M-N Kweon, P-H Kim, H-J Ko, C H Chung
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease, and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism...
August 16, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28810561/cytotoxic-t-lymphocytes-promote-cytarabine-induced-acute-myeloid-leukemia-cell-apoptosis-via-inhibiting-bcl-2-expression
#7
Rui Deng, Fang-Yi Fan, Hai Yi, Li Fu, Yan Zeng, Yi Wang, Xiao-Juan Miao, Yan-Rong Shuai, Guang-Cui He, Yi Su
Acute myeloid leukemia (AML) remains difficult to cure due to its drug tolerance and refractoriness. Immunotherapy is a growing area of cancer research, which has been applied for the treatment of numerous types of cancer, including leukemia. The present study generated AML cell-specific cytotoxic T lymphocytes (CTLs) in vitro and investigated the effect of combining CTL treatment with one of the most commonly used drugs for the treatment of hematological malignancies, cytarabine, on AML cell apoptosis. Firstly, it was observed that monocyte-depleted peripheral blood lymphocytes from healthy donors could be used to generate large numbers of CD3(+)CD8(+) CTLs through immune stimulation...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808733/-basic-principles-signaling-pathways-and-checkpoints
#8
REVIEW
M Preusser
Immune checkpoint inhibitors have shown significant antitumor activity and good tolerability in a number of cancer types and have entered the everyday oncological practice. This article briefly summarizes the mode of action of immune checkpoint inhibitors to provide a basis for the understanding of their clinical activity, radiological response patterns and adverse event profile.
August 14, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28807539/murine-models-for-mucosal-tolerance-in-allergy
#9
REVIEW
Ursula Smole, Irma Schabussova, Winfried F Pickl, Ursula Wiedermann
Immunity is established by a fine balance to discriminate between self and non-self. In addition, mucosal surfaces have the unique ability to establish and maintain a state of tolerance also against non-self constituents such as those represented by the large numbers of commensals populating mucosal surfaces and food-derived or air-borne antigens. Recent years have seen a dramatic expansion in our understanding of the basic mechanisms and the involved cellular and molecular players orchestrating mucosal tolerance...
August 11, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28806756/generic-scalable-and-decentralized-fault-detection-for-robot-swarms
#10
Danesh Tarapore, Anders Lyhne Christensen, Jon Timmis
Robot swarms are large-scale multirobot systems with decentralized control which means that each robot acts based only on local perception and on local coordination with neighboring robots. The decentralized approach to control confers number of potential benefits. In particular, inherent scalability and robustness are often highlighted as key distinguishing features of robot swarms compared with systems that rely on traditional approaches to multirobot coordination. It has, however, been shown that swarm robotics systems are not always fault tolerant...
2017: PloS One
https://www.readbyqxmd.com/read/28804981/lipopolysaccharide-inhibits-hepatic-gluconeogenesis-in-rats-the-role-of-immune-cells
#11
Hiroshi Tanaka, Yoshikazu Nishikawa, Toru Fukushima, Ataru Taniguchi, Yoshihito Fujita, Kinsuke Tsuda, Nobuya Inagaki, Masaya Hosokawa
AIMS/INTRODUCTION: Bacterial septicemia has diverse clinical symptoms including severe hypoglycemia. However, sepsis-induced hypoglycemia has not yet been examined in detail. The aim of the present study is to investigate the mechanisms underlying hypoglycemia in sepsis. MATERIALS AND METHODS: We induced endotoxin shock in rats using lipopolysaccharide (LPS). After an intraperitoneal injection of LPS, we measured gluconeogenesis using the pyruvate tolerance test (PTT)...
August 14, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28804903/targeting-of-tolerogenic-dendritic-cells-towards-heat-shock-proteins-a-novel-therapeutic-strategy-for-autoimmune-diseases
#12
REVIEW
Manon A A Jansen, Rachel Spiering, Femke Broere, Jacob M van Laar, John D Isaacs, Willem van Eden, Catharien M U Hilkens
Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T cell response, while leaving other, protective T cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen...
August 14, 2017: Immunology
https://www.readbyqxmd.com/read/28803690/new-insights-into-non-conventional-epitopes-as-t-cell-targets-the-missing-link-for-breaking-immune-tolerance-in-autoimmune-disease
#13
REVIEW
James Harbige, Martin Eichmann, Mark Peakman
The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases...
August 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28803660/multiple-sclerosis-skin-induced-antigen-specific-immune-tolerance
#14
REVIEW
Paula Wildner, Krzysztof W Selmaj
Multiple sclerosis (MS) is a highly prevalent demyelinating disorder, presumed to be driven by an autoimmune response toward the central nervous system (CNS) components. All currently available treatments modulate the immune system globally and besides the reduction of disease activity, they may also impose considerable disturbances on the immune protective mechanisms. Thus, induction of antigen-specific immune tolerance remains the ultimate goal of MS therapy. Such approach carries promising therapeutic perspectives and, above all, a desirable safety profile...
August 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28802495/the-immunology-of-melanoma
#15
REVIEW
Jennifer S Ko
The relatively high DNA mutational burden in melanoma allows for the creation of potentially "foreign," immune-stimulating neoantigens, and leads to its exceptional immunogenicity. Brisk tumor-infiltrating lymphocytes, a marker of immune editing, confer improved overall survival in melanoma, possibly due to reduced sentinel lymph node spread. Meanwhile, T-cell-stimulating drugs, so-called T-cell checkpoint inhibitors, which reverse peripheral tolerance-dependent tumor escape, have demonstrated unparalleled clinical success in metastatic melanoma...
September 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28801358/il-4-il-13-heteroreceptor-influences-th17-cell-conversion-and-sensitivity-to-regulatory-t-cell-suppression-to-restrain-experimental-allergic-encephalomyelitis
#16
Subhasis Barik, Jason S Ellis, Jason A Cascio, Mindy M Miller, Tobechukwu K Ukah, Alexis N Cattin-Roy, Habib Zaghouani
IL-4 and IL-13 have been defined as anti-inflammatory cytokines that can counter myelin-reactive T cells and modulate experimental allergic encephalomyelitis. However, it is not known whether endogenous IL-4 and IL-13 contribute to the maintenance of peripheral tolerance and whether their function is coordinated with T regulatory cells (Tregs). In this study, we used mice in which the common cytokine receptor for IL-4 and IL-13, namely the IL-4Rα/IL-13Rα1 (13R) heteroreceptor (HR), is compromised and determined whether the lack of signaling by endogenous IL-4 and IL-13 through the HR influences the function of effector Th1 and Th17 cells in a Treg-dependent fashion...
August 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28800092/induced-aberrant-organisms-with-novel-ability-to-protect-intestinal-integrity-from-inflammation-in-an-animal-model
#17
Helieh S Oz
Robust and balanced gut microbiota are required to support health and growth. Overgrowth of gut microbial or pathogens can change ecosystem balance, and compromise gut integrity to initiate gastrointestinal (GI) complications. There is no safe and effective modality against coccidiosis. Antibiotic additives routinely fed to food animals to protect against infection, are entered into the food chain, contaminate food products and pass to the consumers. HYPOTHESIS: induced aberrant organisms possess distinct ultrastructure and are tolerated by immunodeficient-animals yet are non-pathogenic, but immunogenic in various strains of chicks to act as a preventive (vaccine) and eliminating the needs for antibiotic additives...
August 11, 2017: Nutrients
https://www.readbyqxmd.com/read/28799202/immune-tolerance-induced-by%C3%A2-platelet-targeted-factor-viii-gene-therapy-in-hemophilia-a-mice-is-cd4%C3%A2-t-cell-mediated
#18
Y Chen, X Luo, J A Schroeder, J Chen, C K Baumgartner, J Hu, Q Shi
BACKGROUND: Immune responses are a major concern in gene therapy. Our previous studies demonstrated that platelet-targeted FVIII (2bF8) gene therapy together with in vivo drug-selection of transduced cells can rescue the bleeding diathesis and induce immune tolerance in FVIII(null) mice. OBJECTIVE: To investigate whether non-selectable 2bF8 lentiviral vector (LV) for the induction of platelet-FVIII expression is sufficient to induce immune tolerance and how immune tolerance is induced after 2bF8LV gene therapy...
August 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28798999/influence-of-immunostimulant-polysaccharides-nucleic-acids-and-bacillus-strains-on-the-innate-immune-and-acute-stress-response-in-turbots-scophthalmus-maximus-fed-soy-bean-and-wheat-based-diets
#19
V I Fuchs, J Schmidt, M J Slater, B H Buck, D Steinhagen
Immunostimulants are widely applied in aquaculture practice and may have beneficial effects on the immune system and physical functions allowing higher tolerance to stress. In the current study, the impact of four (i-iv) dietary active ingredients on the immune and stress response of turbot was examined in two experiments (I and II). A basal low fish meal (FM; 32%) diet was formulated and supplemented with (i) yeast β-glucan and mannan oligosaccharide (GM), (ii) alginic acid (AC), (iii) yeast nucleotides and RNA (NR), or (iv) Bacillus strains (BS)...
August 10, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28798751/role-of-dendritic-cells-in-inflammation-and-loss-of-tolerance-in-the-elderly
#20
REVIEW
Anshu Agrawal, Sudhanshu Agrawal, Sudhir Gupta
Dendritic cells (DCs) play an important role in advancing age-associated progressive decline in adaptive immune responses, loss of tolerance, and development of chronic inflammation. In aged humans, DCs secrete increased levels of pro-inflammatory cytokines and decreased levels of anti-inflammatory and immune-regulatory cytokines. This may contribute to both chronic inflammation and loss of tolerance in aging. Aged DCs also display increased immune response against self-antigens contributing further to both inflammation and loss of tolerance...
2017: Frontiers in Immunology
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