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oral tolerance immunology

Junichiro Kawamura, Fumiaki Sugiura, Yasushi Sukegawa, Yasumasa Yoshioka, Jin-Ichi Hida, Shoichi Hazama, Kiyotaka Okuno
The safety and immunological responsiveness of a peptide vaccine of ring finger protein 43 and 34-kDa translocase of the outer mitochondrial membrane combined with uracil-tegafur/leucovorin (UFT/LV) was previously demonstrated in metastatic colorectal cancer (CRC) in a phase I clinical trial. To clarify the survival benefit of a peptide vaccine combined with UFT/LV as adjuvant treatment, a phase II clinical trial was conducted involving patients with stage III CRC. All enrolled patients, whose human leukocyte antigen (HLA)-A status was double-blinded, were administered the same regime of a peptide vaccine and UFT/LV chemotherapy...
April 2018: Oncology Letters
Takashi Kei Kishimoto, Roberto A Maldonado
Antigen-specific immune tolerance has been a long-standing goal for immunotherapy for the treatment of autoimmune diseases and allergies and for the prevention of allograft rejection and anti-drug antibodies directed against biologic therapies. Nanoparticles have emerged as powerful tools to initiate and modulate immune responses due to their inherent capacity to target antigen-presenting cells (APCs) and deliver coordinated signals that can elicit an antigen-specific immune response. A wide range of strategies have been described to create tolerogenic nanoparticles (tNPs) that fall into three broad categories...
2018: Frontiers in Immunology
Judy J Brown, Sarah P Short, Jennifer Stencel-Baerenwald, Kelly Urbanek, Andrea J Pruijssers, Nicole McAllister, Mine Ikizler, Gwen Taylor, Pavithra Aravamudhan, Solomiia Khomandiak, Bana Jabri, Christopher S Williams, Terence S Dermody
Several viruses induce intestinal epithelial cell death during enteric infection. However, it is unclear whether pro-apoptotic capacity promotes or inhibits replication in this tissue. We infected mice with two reovirus strains that infect the intestine but differ in the capacity to alter immunological tolerance to new food antigen. Infection with reovirus strain T1L, which induces an inflammatory immune response to fed antigen, is prolonged in the intestine, whereas T3D-RV, which does not induce this response, is rapidly cleared from the intestine...
March 7, 2018: Journal of Virology
Allan McI Mowat
For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins...
February 28, 2018: Nature Reviews. Immunology
Ryo Koda, Hirofumi Watanabe, Masafumi Tsuchida, Noriaki Iino, Kazuo Suzuki, Go Hasegawa, Naofumi Imai, Ichiei Narita
BACKGROUND: Acute tubulointerstitial nephritis (ATIN) has been increasingly recognized as an important manifestation of kidney injury associated with the use of immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4). While the exact pathophysiology remains unknown, corticosteroids are the mainstay of management. CASE PRESENTATION: We describe a 67-year-old man with stage IV non-small-cell lung cancer who developed kidney injury during treatment with the anti-PD-1 antibody nivolumab...
February 27, 2018: BMC Nephrology
Karina Oyarce, Mauricio Campos-Mora, Tania Gajardo-Carrasco, Karina Pino-Lagos
Regulatory T cells (Tregs) are critical players of immunological tolerance due to their ability to suppress effector T cell function thereby preventing transplant rejection and autoimmune diseases. During allograft transplantation, increases of both Treg expansion and generation, as well as their stable function, are needed to ensure allograft acceptance; thus, efforts have been made to discover new molecules that enhance Treg-mediated tolerance and to uncover their mechanisms. Recently, vitamin C (VitC), known to regulate T cell maturation and dendritic cell-mediated T cell polarization, has gained attention as a relevant epigenetic remodeler able to enhance and stabilize the expression of the Treg master regulator gene Foxp3, positively affecting the generation of induced Tregs (iTregs)...
2018: Frontiers in Immunology
Ralf Bartenschlager, Thomas F Baumert, Jens Bukh, Michael Houghton, Stanley M Lemon, Brett D Lindenbach, Volker Lohmann, Darius Moradpour, Thomas Pietschmann, Charles M Rice, Robert Thimme, Takaji Wakita
The development and clinical implementation of direct-acting antivirals (DAAs) has revolutionized the treatment of chronic hepatitis C. Infection with any viral genotype can now be eliminated in more than 95% of patients with short courses of all-oral, well-tolerated drugs, even in those with advanced liver disease and liver transplant recipients. DAAs have proven so successful that some now consider hepatitis C virus (HCV) amenable to eradication, and continued research on the virus of little remaining medical relevance...
February 22, 2018: Virus Research
Enza D' Auria, Chiara Mameli, Cristian Piras, Lucia Cococcioni, Andrea Urbani, Gian Vincenzo Zuccotti, Paola Roncada
Cow's milk allergy (CMA) is one of the most common food allergies, especially during childhood. CMA is an immunological mediated adverse reaction to one or more cow's milk proteins, which are normally harmless to a non-allergic individual, as the result of a failure of oral tolerance. To make a correct diagnosis of CMA and a proper treatment are critical in clinical practice. Application of proteomics along with new bio-informatics tools in the field of food allergy is one of the hot topics presented in recent years...
February 3, 2018: Journal of Proteomics
Ellen Kraig, Leslie A Linehan, Hanyu Liang, Terry Q Romo, Qianqian Liu, Yubo Wu, Adriana D Benavides, Tyler J Curiel, Martin A Javors, Nicolas Musi, Laura Chiodo, Wouter Koek, Jonathan A L Gelfond, Dean L Kellogg
Inhibition of the mechanistic target of rapamycin (mTOR) pathway by rapamycin (RAPA), an FDA-approved immunosuppressive drug used as a clinical therapy to prevent solid organ allograft rejection, enhances longevity in mice. Importantly, RAPA was efficacious even when initiated in relatively old animals, suggesting that mTOR inhibition could potentially slow the progression of aging-associated pathologies in older humans (Harrison et al., 2009; Miller et al., 2011). However, the safety and tolerability of RAPA in older human subjects have not yet been demonstrated...
February 3, 2018: Experimental Gerontology
Narin Ozturk, Dilek Ozturk, Zeliha Pala-Kara, Engin Kaptan, Serap Sancar-Bas, Nurten Ozsoy, Suzan Cinar, Gunnur Deniz, Xiao-Mei Li, Sylvie Giacchetti, Francis Lévi, Alper Okyar
The circadian timing system controls many biological functions in mammals including xenobiotic metabolism, detoxification, cell proliferation, apoptosis and immune functions. Everolimus is a mammalian target of rapamycin inhibitor, whose immunosuppressant properties are both desired in transplant patients and unwanted in cancer patients, where it is indicated for its antiproliferative efficacy. Here we sought whether everolimus circadian timing would predictably modify its immunosuppressive effects so as to optimize this drug through timing...
February 5, 2018: Chronobiology International
Julie Wang, Hugh A Sampson
Food allergy is increasingly common in children, affecting about 4-8%. The mainstays of management remain allergen avoidance and emergency preparedness to treat allergic reactions with emergency medications. Unfortunately, these approaches are unsatisfactory for many patients and their families as the restrictions, constant vigilance and unpredictable severity of allergic reactions negatively impact quality of life. In recent decades, there has been significant interest in developing treatments for food allergy that lead to desensitization in order to increase thresholds for triggering allergic reactions and decrease the risk of reacting to allergen-contaminated food products...
January 25, 2018: Pediatric Allergy and Immunology
Yi-Hsin Lin, Ming-Chieh Yang, Ssu-Hsueh Tseng, Rosie Jiang, Andrew Yang, Emily Farmer, Shiwen Peng, Talia Henkle, Yung-Nien Chang, Chien-Fu Hung, T-C Wu
Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines are available, no effective therapeutic strategies to control active HPV diseases exist. Tumor implantation models are traditionally used to study HPV-associated buccal tumors. However, they fail to address precancerous phases of disease progression and display tumor microenvironments distinct from those observed in patients. Previously, K14-E6/E7 transgenic mouse models have been used to generate spontaneous tumors...
January 23, 2018: Cancer Immunology Research
Paola L Smaldini, Fernando Trejo, José L Cohen, Eliane Piaggio, Guillermo H Docena
Therapeutic tolerance restoration has been proven to modify food allergy in patients and animal models and although sublingual immunotherapy (SLIT) has showed promise, combined therapy may be necessary to achieve a strong and long-term tolerance. In this work, we combined SLIT with systemic administration of IL-2 associated with an anti-IL-2 monoclonal antibody (IL-2/anti-IL-2Ab complex or IL-2C) to reverse the IgE-mediated experimental allergy. Balb/c mice were sensitized with cholera toxin and milk proteins and orally challenged with allergen to elicit hypersensitivity reactions...
January 10, 2018: Allergy
Manuel Weber, Maike Büttner-Herold, Luitpold Distel, Jutta Ries, Patrick Moebius, Raimund Preidl, Carol I Geppert, Friedrich W Neukam, Falk Wehrhan
BACKGROUND: Immunologic factors can promote the progression of oral squamous cell carcinomas (oscc). The phylogenetic highly conserved protein Galectin 3 (Gal3) contributes to cell differentiation and immune homeostasis. There is evidence that Gal3 is involved in the progression of oscc and influences the regulation of macrophage polarization. Macrophage polarization (M1 vs. M2) in solid malignancies like oscc contributes to tumor immune-escape. However, the relationship between macrophage polarization and Gal3 expression in oscc is not yet understood...
December 29, 2017: BMC Cancer
Liusong Yang, Lina Wang, Canjun Zhu, Junguo Wu, Yexian Yuan, Lulu Yu, Yaqiong Xu, Jingren Xu, Tao Wang, Zhengrui Liao, Songbo Wang, Xiaotong Zhu, Ping Gao, Yongliang Zhang, Xiuqi Wang, Qingyan Jiang, Gang Shu
Laminarin, a type of β-glucan isolated from brown seaweeds, exhibits verity of physiological activities, which include immunology modulation and antitumor function. To investigate the effect of laminarin on energy homeostasis, mice were orally administrated with laminarin to test food intake, fat deposition, and glucose homeostasis. Chronically, laminarin treatment significantly decreases high-fat-diet-induced body weight gain and fat deposition and reduces blood glucose level and glucose tolerance. Acutely, laminarin enhances serum glucagon-like peptide-1 (GLP-1) content and the mRNA expression level of proglucagon and prohormone convertase 1 in ileum...
November 21, 2017: Oncotarget
Jose Matías, Melibea Berzosa, Yadira Pastor, Juan M Irache, Carlos Gamazo
The immunology of pregnancy is an evolving consequence of multiple reciprocal interactions between the maternal and the fetal-placental systems. The immune response must warrant the pregnancy outcome (including tolerance to paternal antigens), but at the same time, efficiently respond to pathogenic challenges. Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. This review aims to give an overview of the current rationale on the maternal vaccination strategies for the protection of the newborn pig against ETEC...
December 6, 2017: Vaccines
David M Asmuth, John E Hinkle, Anthony LaMarca, Carl J Fichtenbaum, Ma Somsouk, Netanya S Utay, Audrey L Shaw, Bryon W Petschow, Christopher J Detzel, Eric M Weaver
Objectives To evaluate serum-derived bovine immunoglobulin/protein isolate (SBI) for safety and impact on gastrointestinal (GI) symptoms in HIV patients with chronic idiopathic diarrhea. Methods A multi-center trial comprised of a double-blind, placebo (PBO)-controlled lead-in phase, (participants received PBO or SBI at 2.5 or 5.0 g BID for 4 weeks) followed by a 20-week, PBO-free phase (SBI at either 2.5 or 5.0 g BID). Participants included HIV-infected patients who were virologically suppressed with a history of chronic idiopathic diarrhea, defined as > 3 loose stools per day for ≥ 3 months without an identifiable cause...
November 2017: HIV Clinical Trials
Adna Luciana Souza, Sarah Leão Fiorini Aguiar, Mariana Camila Gonçalves Miranda, Luisa Lemos, Mauro Andrade Freitas Guimaraes, Daniela Silva Reis, Patrícia Aparecida Vieira Barros, Emerson Soares Veloso, Toniana Gonçalves Carvalho, Fabiola Mara Ribeiro, Enio Ferreira, Denise Carmona Cara, Ana Cristina Gomes-Santos, Ana Maria Caetano Faria
Dietary proteins can influence the maturation of the immune system, particularly the gut-associated lymphoid tissue, when consumed from weaning to adulthood. Moreover, replacement of dietary proteins by amino acids at weaning has been shown to impair the generation of regulatory T cells in the gut as well as immune activities such as protective response to infection, induction of oral and nasal tolerance as well as allergic responses. Polymeric and elemental diets are used in the clinical practice, but the specific role of intact proteins and free amino acids during the intestinal inflammation are not known...
2017: Frontiers in Immunology
G B Pajno, M Fernandez-Rivas, S Arasi, G Roberts, C A Akdis, M Alvaro-Lozano, K Beyer, C Bindslev-Jensen, W Burks, M Ebisawa, P Eigenmann, E Knol, K C Nadeau, L K Poulsen, R van Ree, A F Santos, G du Toit, S Dhami, U Nurmatov, Y Boloh, M Makela, L O'Mahony, N Papadopoulos, C Sackesen, I Agache, E Angier, S Halken, M Jutel, S Lau, O Pfaar, D Ryan, G Sturm, E-M Varga, R G van Wijk, A Sheikh, A Muraro
Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT...
September 27, 2017: Allergy
Milena Sokolowska, Cezmi A Akdis
Several recent key findings in immunology of allergic diseases that have led to a need of reassessment of our current thinking are reviewed in this issue of the journal. Recently developed strong evidence on the role of hygiene hypothesis in protection from allergic disease and its immune mechanisms is reviewed by Ober et al. The authors pointed out immunologic mechanisms of lower prevalence of asthma and allergic sensitization observed among Amish children living on traditional farms with higher endotoxin levels as compared to Hutterite children living on industrialized farms...
October 2017: Current Opinion in Immunology
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