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oral tolerance immunology

Ana Brotons-Canto, Nekane Martín-Arbella, Carlos Gamazo, Juan M Irache
Allergic diseases constitute one of the most common causes of chronic illness in developed countries. The main mechanism determining allergy is an imbalance between Th1 and Th2 response towards Th2. Areas covered: This review describes the mechanisms underlying the natural tolerance to food components and the development of an allergic response in sensitized individuals. Furthermore, therapeutic approaches proposed to manage these abnormal immunologic responses food are also presented and discussed. Expert opinion: In the past, management of food allergies has consisted of the education of patients to avoid the ingestion of the culprit food and to initiate the therapy (e...
October 12, 2016: Expert Opinion on Drug Delivery
M A van Leeuwen, L M M Costes, L A van Berkel, Y Simons-Oosterhuis, M F du Pré, A E Kozijn, H C Raatgeep, D J Lindenbergh-Kortleve, N van Rooijen, F Koning, J N Samsom
Celiac disease is caused by inflammatory T-cell responses against the insoluble dietary protein gliadin. We have shown that, in humanized mice, oral tolerance to deamidated chymotrypsin-digested gliadin (CT-TG2-gliadin) is driven by tolerogenic interferon (IFN)-γ- and interleukin (IL)-10-secreting type 1 regulatory T-like cells (Tr1-like cells) generated in the spleen but not in the mesenteric lymph nodes. We aimed to uncover the mechanisms underlying gliadin-specific Tr1-like-cell differentiation and hypothesized that proteolytic gliadin degradation by splenic macrophages is a decisive step in this process...
August 31, 2016: Mucosal Immunology
Yu Lei, Yuying Xie, Yee Sun Tan, Mark E Prince, Jeffrey S Moyer, Jacques Nör, Gregory T Wolf
Evidence gleaned from recent studies on the role of tumor-infiltrating lymphocytes (TILs) suggests that cancer is not only a genetic disease but also an immunologic disease. Head and Neck Squamous Cell Carcinoma (HNSCC) has been a significant model to study cancer cell-immune cell interactions. First, immune cell infiltration is an important feature of these tumors. Second, HNSCC frequently develops resistance to immunogenic cytotoxicity, which provides a window to decipher how tumors engage the immune system to establish immune tolerance...
October 2016: Oral Oncology
J H Fine, G S Bondy, L Coady, B Pearce, N Ross, A F Tayabali, S Halappanavar, D Caldwell, I Curran, D E Lefebvre
Humans could become exposed to carbon black nanoparticles (CBNPs) in consumer products or an occupational setting. In rodent models, acute respiratory, subcutaneous, and direct immune cell exposure to CBNPs has been shown to enhance allergic sensitization to co-administered ovalbumin (OVA) protein from chicken egg. However, little is known about the effects of ingested CBNPs on immunological responses and oral tolerance to food antigens. We hypothesized that ingestion of CBNPs would enhance the development of food allergy to OVA...
August 18, 2016: Nanotoxicology
Claudia Petrarca, Emanuela Clemente, Valentina Amato, Alessia Gatta, Sara Cortese, Alessia Lamolinara, Cosmo Rossi, Stefania Zanotta, Gianni Mistrello, Roberto Paganelli, Mario Di Gioacchino
BACKGROUND: Airborne allergens can induce an immunological chronic disease characterized by airway hyper responsiveness and inflammation, mediated by exaggerated Th2 immune response. Allergen-specific immunotherapy (AIT) is effective for treating this condition because it is able to modify its natural course by opposing the underlying pathogenic mechanisms and determining immune suppression, immune deviation and tolerance. The rational for the present study was to investigate the possibility of improving allergoid-based IT in terms of efficacy and safety...
2016: Clinical and Molecular Allergy: CMA
Andrea Picchianti Diamanti, M Manuela Rosado, Bruno Laganà, Raffaele D'Amelio
BACKGROUND: Only recently, the scientific community gained insights on the importance of the intestinal resident flora for the host's health and disease. Gut microbiota in fact plays a crucial role in modulating innate and acquired immune responses and thus interferes with the fragile balance inflammation versus tolerance. MAIN BODY: Correlations between gut bacteria composition and the severity of inflammation have been studied in inflammatory bowel diseases. More recently similar alterations in the gut microbiota have been reported in patients with spondyloarthritis, whereas in rheumatoid arthritis an accumulating body of evidence evokes a pathogenic role for the altered oral microbiota in disease development and course...
August 4, 2016: Journal of Translational Medicine
Diana Pérez-Alzate, Natalia Blanca-López, Inmaculada Doña, José A Agúndez, Elena García-Martín, José A Cornejo-García, James R Perkins, Miguel Blanca, Gabriela Canto
In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA)...
2016: Frontiers in Pharmacology
Lieqi Tang, Catherine Y Cheng, Xiangrong Sun, Alexandra J Pedicone, Mansour Mohamadzadeh, Sam X Cheng
Different from other epithelia, the intestinal epithelium has the complex task of providing a barrier impeding the entry of toxins, food antigens, and microbes, while at the same time allowing for the transfer of nutrients, electrolytes, water, and microbial metabolites. These molecules/organisms are transported either transcellularly, crossing the apical and basolateral membranes of enterocytes, or paracellularly, passing through the space between enterocytes. Accordingly, the intestinal epithelium can affect energy metabolism, fluid balance, as well as immune response and tolerance...
2016: Frontiers in Physiology
Jin-Ok Baek, Joo-Young Roh, YunJae Jung
BACKGROUND: Oral tolerance is immune unresponsiveness induced by oral administration of innocuous antigens. Oral administration of allergens has been shown to be effective for suppressing IgE production in allergic responses. However, whether oral tolerance has a role in protection from allergic skin inflammation has not been fully investigated. Here, we evaluated the potential protective role of oral tolerance in a murine model of atopic dermatitis (AD) and investigated the underlying immunologic mechanisms...
June 21, 2016: Allergy
Varvara A Kirchner, Erik B Finger, Melena D Bellin, Ty B Dunn, Rainer W G Gruessner, Bernhard J Hering, Abhinav Humar, Aleksandra K Kukla, Arthur J Matas, Timothy L Pruett, David E R Sutherland, Raja Kandaswamy
BACKGROUND: Living donor segmental pancreas transplants (LDSPTx) have been performed selectively to offer a preemptive transplant option for simultaneous pancreas-kidney recipients and to perform a single operation decreasing the cost of pancreas after kidney transplant. For solitary pancreas transplants, this option historically provided a better immunologic match. Although short-term donor outcomes have been documented, there are no long-term studies. METHODS: We studied postdonation outcomes in 46 segmental pancreas living donors...
June 2016: Transplantation
Tsuguto Toda, Shin Yoshino
The mucosal immune system is exposed to non-self antigens in food and the gut microbiota. Therefore, the recognition of orally ingested non-self antigens is suppressed in healthy individuals to avoid excessive immune responses in a process called "oral tolerance". The breakdown of oral tolerance has been cited as a possible cause of food allergy, and amorphous silica nanoparticles (nSP) have been implicated in this breakdown. As nSP are widely used in foodstuffs and other products, exposure to them is increasing; thus, investigations of any effects of nSP on oral tolerance are urgent...
September 2016: Journal of Immunotoxicology
Jeng-Chang Chen, Cheng-Chi Chan, Chia-Jen Wu, Liang-Shiou Ou, Hsiu-Yueh Yu, Hsueh-Ling Chang, Li-Yun Tseng, Ming-Ling Kuo
RATIONALE: Actively acquired tolerance occurs when foreign antigens come into contact with the immature fetal immune system. OBJECTIVES: Armed with the knowledge of actively acquired tolerance, we attempted to prenatally abolish or diminish allergic responses. METHODS: In utero injection of adjuvant-free ovalbumin (OVA) was conducted in gestational day 14 FVB/N fetuses. Postnatally, mice were evaluated for their resistance to intraperitoneal OVA sensitization and oral or aerosolized OVA challenge, and examined for humoral and cellular immunological profiles, airway hyperresponsiveness to bronchospastic stimuli, and lung histology...
April 11, 2016: American Journal of Respiratory and Critical Care Medicine
Vincent Dioszeghy, Lucie Mondoulet, Emilie Puteaux, Véronique Dhelft, Mélanie Ligouis, Camille Plaquet, Christophe Dupont, Pierre-Henri Benhamou
Allergen-specific immunotherapy has been proposed as an attractive strategy to actively treat food allergy using the following three different immunotherapy routes: oral (OIT), sublingual (SLIT) and epicutaneous (EPIT) immunotherapy. Regulatory T cells (Tregs) have been shown to have a pivotal role in the mechanisms of immunotherapy. The aim of this study was to compare the phenotype and function of Tregs induced in peanut-sensitized BALB/c mice using these three routes of treatment. We show that although EPIT, OIT and SLIT were all able to effectively desensitize peanut-sensitized mice, they induced different subsets of Tregs...
April 11, 2016: Cellular & Molecular Immunology
P M Gamboa, E Garcia-Lirio, C Gonzalez, A Gonzalez, Martinez-Aranguren R M, L Sanz María
OBJECTIVES: To assess modifications in baseline specific IgE- and anti-IgE- and antigen-specific-mediated basophil activation in egg-allergic children. The values were compared before and after the children completed specific oral tolerance induction (SOTI) with egg. PATIENTS AND METHODS: We studied 28 egg-allergic children who completed SOTI with egg. The basophil activation test and specific IgE determinations with egg white, ovalbumin, and ovomucoid were performed in all 28 children...
2016: Journal of Investigational Allergology & Clinical Immunology
Stephanie A Leonard
Baked milk and egg have the potential to act as a form of oral immunotherapy (OIT). Clinical studies have shown that a majority of milk- and egg-allergic children can tolerate these allergens modified in baked form, and immunologic changes reported in subjects ingesting baked milk and egg mirror those seen in food allergy OIT trials. In addition, several studies have indicated that resolution of milk and egg allergies occur sooner in populations regularly ingesting baked milk and egg. Oral food challenges remain the best method for determining tolerability of baked milk and egg since baseline characteristics and diagnostic testing have not been reliable predictors...
April 2016: Current Allergy and Asthma Reports
Tuuli Ranki, Sari Pesonen, Akseli Hemminki, Kaarina Partanen, Kalevi Kairemo, Tuomo Alanko, Johan Lundin, Nina Linder, Riku Turkki, Ari Ristimäki, Elke Jäger, Julia Karbach, Claudia Wahle, Matti Kankainen, Charlotta Backman, Mikael von Euler, Elina Haavisto, Tiina Hakonen, Raita Heiskanen, Magnus Jaderberg, Juuso Juhila, Petri Priha, Laura Suoranta, Lotta Vassilev, Antti Vuolanto, Timo Joensuu
BACKGROUND: We conducted a phase I study with a granulocyte macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, ONCOS-102, in patients with solid tumors refractory to available treatments. The objectives of the study were to determine the optimal dose for further use and to assess the safety, tolerability and adverse event (AE) profile of ONCOS-102. Further, the response rate and overall survival were evaluated as well as preliminary evidence of disease control...
2016: Journal for Immunotherapy of Cancer
Tae Won Song
Food allergy is common and sometimes life threatening for Korean children. The current standard treatment of allergen avoidance and self-injectable epinephrine does not change the natural course of food allergy. Recently, oral, sublingual, and epicutaneous immunotherapies have been studied for their effectiveness against food allergy. While various rates of desensitization (36% to 100%) and tolerance (28% to 75%) have been induced by immunotherapies for food allergy, no single established protocol has been shown to be both effective and safe...
February 2016: Korean Journal of Pediatrics
Dan-Xia Fei, Qing-Mei Liu, Feng Chen, Yang Yang, Zhong-Wei Chen, Min-Jie Cao, Guang-Ming Liu
SCOPE: The enzymatic cross-linking of an allergen by food processing may alter its sensitization potential. In this study, the IgE-binding activity and allergenicity of cross-linked thermal polymerized arginine kinase (CL-pAK) were investigated. METHODS AND RESULTS: The IgE-binding activity and stability of CL-pAK were analyzed by immunological and proteomics methods. The sensitization and potency to induce oral tolerance of CL-pAK were tested using in vivo assays and a cell model...
July 2016: Molecular Nutrition & Food Research
Stacie M Jones, A Wesley Burks, Corinne Keet, Brian P Vickery, Amy M Scurlock, Robert A Wood, Andrew H Liu, Scott H Sicherer, Alice K Henning, Robert W Lindblad, Peter Dawson, Cecilia Berin, David M Fleischer, Donald Y M Leung, Marshall Plaut, Hugh A Sampson
BACKGROUND: We previously reported the results of a randomized placebo-controlled study of egg oral immunotherapy (eOIT) in which 27.5% of subjects achieved sustained unresponsiveness (SU) after 2 years. Here we report the results of treatment through 4 years and long-term follow-up. OBJECTIVE: We sought to evaluate the efficacy and safety of eOIT in participants treated up to 4 years. METHODS: Children with egg allergy (5-18 years old) received eOIT (n = 40) for up to 4 years or placebo (n = 15) for 1 year or less...
April 2016: Journal of Allergy and Clinical Immunology
María Teresa Julián, Núria Alonso, Roger Colobran, Alex Sánchez, Antoni Miñarro, Irma Pujol-Autonell, Jorge Carrascal, Silvia Rodríguez-Fernández, Rosa María Ampudia, Marta Vives-Pi, Manel Puig-Domingo
The transmembrane glycoprotein CD26 or dipeptidyl peptidase IV (DPPIV) is a multifunctional protein. In immune system, CD26 plays a role in T-cell function and is also involved in thymic maturation and emigration patterns. In preclinical studies, treatment with DPPIV inhibitors reduces insulitis and delays or even reverses the new -onset of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. However, the specific mechanisms involved in these effects remain unknown. The aim of the present study was to investigate how DPPIV inhibition modifies the expression of genes in the thymus of NOD mice by microarray analysis...
May 5, 2016: Molecular and Cellular Endocrinology
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