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Immune suppression

Jeremy A Goettel, Roopali Gandhi, Jessica E Kenison, Ada Yeste, Gopal Murugaiyan, Sharmila Sambanthamoorthy, Alexandra E Griffith, Bonny Patel, Dror S Shouval, Howard L Weiner, Scott B Snapper, Francisco J Quintana
Existing therapies for inflammatory bowel disease that are based on broad suppression of inflammation result in variable clinical benefit and unwanted side effects. A potential therapeutic approach for promoting immune tolerance is the in vivo induction of regulatory T cells (Tregs). Here we report that activation of the aryl hydrocarbon receptor using the non-toxic agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces human Tregs in vitro that suppress effector T cells through a mechanism mediated by CD39 and Granzyme B...
October 25, 2016: Cell Reports
Chwan Hong Foo, Christina L Rootes, Karla Cowley, Glenn A Marsh, Cathryn M Gould, Celine Deffrasnes, Christopher J Cowled, Reuben Klein, Sarah J Riddell, Deborah Middleton, Kaylene J Simpson, Lin-Fa Wang, Andrew G D Bean, Cameron R Stewart
Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are bat-borne viruses that cause fatal disease in humans and a range of other mammalian species. Gaining a deeper understanding of host pathways exploited by henipaviruses for infection may identify targets for new anti-viral therapies. Here we have performed genome-wide high-throughput agonist and antagonist screens at biosafety level 4 to identify host-encoded microRNAs (miRNAs) impacting henipavirus infection in human cells. Members of the miR-181 and miR-17~93 families strongly promoted Hendra virus infection...
October 2016: PLoS Pathogens
Annabelle Cikankowitz, Anne Clavreul, Clément Tétaud, Laurent Lemaire, Audrey Rousseau, Nicolas Lepareur, Djamel Dabli, Francis Bouchet, Emmanuel Garcion, Philippe Menei, Olivier Couturier, François Hindré
Internal radiation strategies hold great promise for glioblastoma (GB) therapy. We previously developed a nanovectorized radiotherapy that consists of lipid nanocapsules loaded with a lipophilic complex of Rhenium-188 (LNC(188)Re-SSS). This approach resulted in an 83 % cure rate in the 9L rat glioma model, showing great promise. The efficacy of LNC(188)Re-SSS treatment was optimized through the induction of a T-cell immune response in this model, as it is highly immunogenic. However, this is not representative of the human situation where T-cell suppression is usually encountered in GB patients...
October 25, 2016: Journal of Neuro-oncology
María de Lourdes Mora-García, Rosario García-Rocha, Omar Morales-Ramírez, Juan José Montesinos, Benny Weiss-Steider, Jorge Hernández-Montes, Luis Roberto Ávila-Ibarra, Christian Azucena Don-López, Marco Antonio Velasco-Velázquez, Vianey Gutiérrez-Serrano, Alberto Monroy-García
BACKGROUND: In recent years, immunomodulatory mechanisms of mesenchymal stem/stromal cells (MSCs) from bone marrow and other "classic" sources have been described. However, the phenotypic and functional properties of tumor MSCs are poorly understood. The aim of this study was to analyze the immunosuppressive capacity of cervical cancer-derived MSCs (CeCa-MSCs) on effector T lymphocytes through the purinergic pathway. METHODS: We determined the expression and functional activity of the membrane-associated ectonucleotidases CD39 and CD73 on CeCa-MSCs and normal cervical tissue-derived MSCs (NCx-MSCs)...
October 26, 2016: Journal of Translational Medicine
Paolo Lissoni
Despite its apparent failure in cancer therapy, IL-2 still remains fundamental in the activation of antitumor immunity. Areas covered: The aim of this review is the reinterpretation of the role of IL-2 in anticancer immunity, according to knowledge gained of the cytokine network, by highlighting its importance in inducing T helper-1 (TH1) cell proliferation, natural killer (NK) actHivation and IL-12 secretion. However, its main negative effect is the stimulation of regulatory T cells (Tregs), which in contrast suppresses anticancer immunity...
October 26, 2016: Expert Review of Clinical Immunology
Matthew J Delano, Peter A Ward
Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses. With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after "recovery" from acute events...
November 2016: Immunological Reviews
Enrico Girardi, Antonella d'Arminio Monforte, Laura Camoni, Patrizio Pezzotti, Giovanni Guaraldi, Adriana Ammassari, Andrea Antinori, Stefano Bonora, Cristina Mussini, Antonella Cingolani, Giulio Maria Corbelli, Silvia Adami, Luca Degli Esposti, Margherita Andretta
HIV disease has dramatically changed in the last two decades from a progressive, lethal disease to a chronic manageable condition. These changes are due to the availability of potent antiretroviral combination therapy, which also have the potential to contribute significantly to the control of the epidemic. Among persons living with HIV, incidence of immunosuppression-related opportunistic illnesses has clearly decreased, while an increase was observed in the prevalence of age-related noncommunicable comorbidities, including cardiovascular, metabolic, renal, bone and hepatic disease, due to chronic inflammatory state and to an overall aging of the population of persons with HIV...
October 2016: Recenti Progressi in Medicina
Yang Yu, Yan Liu, Chen Zong, Qingbo Yu, Xue Yang, Lei Liang, Fei Ye, Li Nong, Yuxian Jia, Yongkui Lu, Zhipeng Han
Mesenchymal stem cells (MSCs) are generally used in regenerative medicine, tissue engineering and therapy for immune disorder diseases. However, due to the immunosuppressive function of MSCs, the application of MSCs in breast cancer therapy remains limited. Sirt1 is the closest mammalian homologue of the yeast enzyme Sir2 which has an established capacity to influence yeast replicative lifespan. In this study, we demonstrated the effect of MSCs with Sirt1 overexpression (MSCs-Sirt1) in mice bearing 4T1 breast cancer and investigated the underlying mechanism...
October 26, 2016: Scientific Reports
I Na Yoon, Ji Hong, Peng Zhang, Jae Sam Hwang, Ho Kim
We previously reported that the CopA3 peptide (LLCIALRKK, D-form) originally isolated from the Korean dung beetle has antimicrobial and immunosuppressive effects. However, the high cost of producing the synthetic peptide, especially the D-form, has limited the development of CopA3 for therapeutic purposes. Here, we investigated whether the CopA3 deletion derivative, CopA5, which is composed of only five amino acids (LLCIA) and has the L-form structure, could inhibit the lipopolysaccharide (LPS)-induced activation of macrophages...
October 25, 2016: Journal of Microbiology and Biotechnology
Susan Yung, Claudia Yc Ng, Kin Yi Au, Kwok Fan Cheung, Qing Zhang, Chenzhu Zhang, Desmond Yh Yap, Mel Km Chau, Tak Mao Chan
Immune deposits are often observed along the tubular basement membrane in patients with lupus nephritis, but the role of anti-dsDNA antibody deposition on tubulo-interstitial inflammation remains to be investigated. We examined the effect of human polyclonal anti-dsDNA antibodies on inflammatory processes in cultured proximal renal tubular epithelial cells (HK-2 cells) and their association with serum levels of IL-6, IL-8 and MCP-1 in patients. Binding of anti-dsDNA antibodies to HK-2 cells was investigated by cellular ELISA, flow cytometry and immunohistochemistry...
October 25, 2016: Clinical Science (1979-)
C A Pope, Aruni Bhatnagar, James McCracken, Wesley T Abplanalp, Daniel J Conklin, Timothy E O'Toole
RATIONALE: Epidemiologic evidence indicates that exposures to fine particulate matter air pollution (PM2.5) contribute to global burden of disease, primarily as a result of increased risk of cardiovascular morbidity and mortality. However, mechanisms by which PM2.5 exposure induces cardiovascular injury remain unclear. PM2.5-induced endothelial dysfunction and systemic inflammation have been implicated, but direct evidence is lacking. OBJECTIVE: To examine whether acute exposure to PM2...
October 25, 2016: Circulation Research
Iara P Calil, Elizabeth P B Fontes
BACKGROUND: Among the environmental limitations that affect plant growth, viruses cause major crop losses worldwide and represent serious threats to food security. Significant advances in the field of plant-virus interactions have led to an expansion of potential strategies for genetically engineered resistance in crops during recent years. Nevertheless, the evolution of viral virulence represents a constant challenge in agriculture that has led to a continuing interest in the molecular mechanisms of plant-virus interactions that affect disease or resistance...
October 24, 2016: Annals of Botany
Roberta Cirincione, Federica Maria Di Maggio, Giusi Irma Forte, Luigi Minafra, Valentina Bravatà, Laura Castiglia, Vincenzo Cavalieri, Giovanni Borasi, Giorgio Russo, Domenico Lio, Cristina Messa, Maria Carla Gilardi, Francesco Paolo Cammarata
In recent years, high-intensity focused ultrasound (HIFU) has emerged as a new and promising non-invasive and non-ionizing ablative technique for the treatment of localized solid tumors. Extensive pre-clinical and clinical studies have evidenced that, in addition to direct destruction of the primary tumor, HIFU-thermoablation may elicit long-term systemic host anti-tumor immunity. In particular, an important consequence of HIFU treatment includes the release of tumor-associated antigens (TAAs), the secretion of immuno-suppressing factors by cancer cells and the induction of cytotoxic T lymphocyte (CTL) activity...
October 22, 2016: Ultrasound in Medicine & Biology
M Tashani, M Alfelali, O Barasheed, A S Alqahtani, L Heron, M Wong, H Rashid, R Booy
Sequential or co-administration of vaccines has potential to alter the immune response to any of the antigens. Existing literature suggests that prior immunisation of tetanus/diphtheria-containing vaccines can either enhance or suppress immune response to conjugate pneumococcal or meningococcal vaccines. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage 2014. We also investigated tolerability of these vaccines separately and concomitantly. We randomly assigned each participant to one of three vaccination schedules...
October 22, 2016: Vaccine
Sandra Maria Barbalho, Marcelo Dib Bechara, Ricardo de Alvares Goulart, Karina Quesada, Rodrigo Galhardi Gasparini, Antonely de Cássio Alves de Carvalho, Adriana Maria Ragassi Fiorini
Ulcerative colitis and Crohn's disease are two major forms of the inflammatory bowel diseases (IBDs). Vitamin A (VA) and vitamin D (VD) may be associated with reduction in inflammation in these disorders. The aim of this review was to show the current evidence that may associate VA and VD with IBDs. Data linking VA, VD, and IBDs were studied. Both VA and VD may be related to the immune system in different manners. The active form of VA, retinoic acid, may be related to the growth factor-β and release of interleukin-10 (IL-10), thus involved with the resolution of the inflammation...
October 25, 2016: Journal of Medicinal Food
Zhenhua Zhang, Li Liu, Chunliang Liu, Shousong Cao, Yizhun Zhu, Qibing Mei
Breast cancer is the second leading cause of cancer‑related deaths in female patients, and the main reasons are late diagnosis, limited therapeutic options and metastasis. Therefore, development of molecular therapeutic targets for breast cancer to suppress tumorigenesis, growth and metastasis may improve the therapeutic options and be of great benefit to patients. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a novel molecule for maintaining immune homeostasis and is involved in cancer development...
October 21, 2016: Oncology Reports
Da Hae Lee, Bart Keymeulen, Robert Hilbrands, Zhidong Ling, Ursule Van de Velde, Daniel Jacobs-Tulleneers-Thevissen, Geert Maleux, Bruno Lapauw, Laurent Crenier, Christophe De Block, Chantal Mathieu, Daniel Pipeleers, Pieter Gillard
BACKGROUND: Induction therapy with a T cell depleting agent followed by mycophenolate mofetil (MMF) and tacrolimus (Tac) is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. METHODS: Fifty-one patients (ages between 29-63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin (ATG)-MMF-Tac protocol...
October 25, 2016: Transplantation
Wen Zhang, Fujian Zhao, Deqiu Huang, Xiaoling Fu, Xian Li, Xiaofeng Chen
Host immune response induced by foreign bone biomaterials plays an important role in determining their fate after implantation. Hence, it is well worth designing advanced bone substitute materials with beneficial immunomodulatory properties to modulate the host-material interactions. Bioactive glasses (BG), with excellent osteoconductivity and osteoinductivity, are regarded as important biomaterials in the field of bone regeneration. In order to explore a novel BG-based osteoimmunomodulatory implant with the capacity of potentially enhancing bone regeneration, it is a possible way to regulate the local immune microenvironment through manipulating macrophage polarization...
October 25, 2016: ACS Applied Materials & Interfaces
E Semik, A Gurgul, T Ząbek, K Ropka-Molik, C Koch, K Mählmann, M Bugno-Poniewierska
Equine sarcoids are the most commonly detected skin tumours in Equidae. In the present research, a comparative transcriptomic analysis was performed which aimed at looking inside a tumour biology and identification of the expression profile as a potential source of cancer specific genes useful as biomarkers. We have used Horse Gene Expression Microarray data from matched equine sarcoids and tumour-distant skin samples. In total, 901 significantly differentially expressed genes (DEGs) between lesional and healthy skin samples have been identified (fold change ≥ 2; P < 0...
October 25, 2016: Veterinary and Comparative Oncology
Y Ilan
BACKGROUND: The systemic immune system plays a role in inflammation and fibrogenesis associated with non-alcoholic steatohepatitis (NASH) and has become a potential target for drug development. In particular, the gut immune system has been suggested as a means for generating signals that can target the systemic immune system. AIM: To describe seven novel methods being developed for the treatment of NASH that target the gut immune system for alleviation of the systemic inflammatory response, including oral administration of fatty-liver-derived proteins, anti-CD3 antibodies, tumour necrosis factor fusion protein, anti-lipopolysaccharide antibodies, glucosylceramide, delayed-release mercaptopurine, and soy-derived extracts...
October 24, 2016: Alimentary Pharmacology & Therapeutics
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