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https://www.readbyqxmd.com/read/29038654/cpg-odn-facilitates-effective-intratracheal-immunization-and-recall-of-memory-against-neoantigen-expressing-alveolar-cells
#1
Mathias Riehn, Marcin Cebula, Hansjörg Hauser, Dagmar Wirth
Intrapulmonary immune reactions are impaired by the tolerogenic environment of the lung. This is manifested by the absence of effective endogenous T cell responses upon neoantigen expression. This tolerance is considered to contribute to lung cancer and inefficient immune therapeutic interventions. To investigate the mechanisms contributing to lung tolerance and to overcome these restrictions, we developed a transgenic mouse model with induction of a neoantigen (OVA) exclusively in alveolar type II epithelial cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033938/early-life-nutritional-factors-and-mucosal-immunity-in-the-development-of-autoimmune-diabetes
#2
REVIEW
Ling Xiao, Belinda Van't Land, Wouter R P H van de Worp, Bernd Stahl, Gert Folkerts, Johan Garssen
Type 1 diabetes (T1D) is an immune-mediated disease with a strong genetic basis but might be influenced by non-genetic factors such as microbiome development that "programs" the immune system during early life as well. Factors influencing pathogenesis, including a leaky intestinal mucosal barrier, an aberrant gut microbiota composition, and altered immune responsiveness, offer potential targets for prevention and/or treatment of T1D through nutritional or pharmacologic means. In this review, nutritional approaches during early life in order to protect against T1D development have been discussed...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29018059/involvement-of-leptin-in-the-molecular-physiology-of-the-placenta
#3
Malena Schanton, Julieta Lorena Maymó, Antonio Pérez-Pérez, Victor Sanchez-Margalet, Cecilia Varone
Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53 master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placental stimuli. The expression of leptin in placenta is regulated by hCG, insulin, steroids, hypoxia, and many other growth hormones, suggesting that it might have an important endocrine function in the trophoblastic cells...
October 9, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28990401/reactive-oxygen-species-and-their-implications-on-cd4-t-cells-in-type-1-diabetes
#4
Dana M Previte, Jon D Piganelli
Previous work has indicated that Type 1 diabetes (T1D) pathology is highly driven by reactive oxygen species (ROS). One way in which ROS shape the autoimmune response demonstrated in T1D is by promoting CD4+ T cell activation and differentiation. As CD4+ T cells are a significant contributor to pancreatic cell destruction in T1D, understanding how ROS impact their development, activation, and differentiation is critical. Recent advances: CD4+ T cells themselves generate ROS via NADPH oxidase expression and electron transport chain activity...
October 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28985848/transforming-growth-factor-%C3%AE-1-and-fas-ligand-synergistically-enhance-immune-tolerance-in-dendritic-cells-in-liver-transplantation
#5
Minglian Qiu, Yujuan Chen, Lihong Chen, Jinhua Zeng, Jingfeng Liu
BACKGROUND: Long-term survival of patients following liver transplantation can be achieved by application of genetically modified, immune tolerogenic immature dendritic cells (imDCs) to overcome allograft-induced acute cellular rejection, a major cause of death. In this study, using a rat model of liver transplantation, we determined whether cotransfection of transforming growth factor β1 (TGF-β1) and Fas ligand (FasL) in imDCs synergistically enhances immune tolerance. MATERIALS AND METHODS: We first determined the immune tolerogenic effects of TGF-β1 and FasL independently or together in imDCs by measuring the levels of CD86 and CD80 and by assessing T-cell proliferation using mixed lymphocyte reaction tests...
October 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28978469/prostaglandin-e2-leads-to-the-acquisition-of-dnmt3a-dependent-tolerogenic-functions-in-human-myeloid-derived-suppressor-cells
#6
Javier Rodríguez-Ubreva, Francesc Català-Moll, Nataša Obermajer, Damiana Álvarez-Errico, Ricardo N Ramirez, Carlos Company, Roser Vento-Tormo, Gema Moreno-Bueno, Robert P Edwards, Ali Mortazavi, Pawel Kalinski, Esteban Ballestar
Myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) arise from common progenitors. Tumor-derived factors redirect differentiation from immune-promoting DCs to tolerogenic MDSCs, an immunological hallmark of cancer. Indeed, in vitro differentiation of DCs from human primary monocytes results in the generation of MDSCs under tumor-associated conditions (PGE2 or tumor cell-conditioned media). Comparison of MDSC and DC DNA methylomes now reveals extensive demethylation with specific gains of DNA methylation and repression of immunogenic-associated genes occurring in MDSCs specifically, concomitant with increased DNA methyltransferase 3A (DNMT3A) levels...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28970672/extracorporeal-photopheresis-review-of-technical-aspects
#7
REVIEW
Satyam Arora, Rasika Setia
Extracorporeal photochemotherapy (ECP) is considered as an immune modulating therapy majorly targeting the T cells of the Immune system. ECP induces an anti-inflammatory condition with tolerogenic responses without inducing a global immunosuppression state which is a typical feature of other therapeutic options such as steroids. Clinical indication of ECP has grown over time since its initial applications. Our review discusses the technical aspects of the concept of photopheresis with the available methods for its clinical applications...
July 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28962099/indoleamine-2-3-dioxygenase-and-inducible-nitric-oxide-synthase-mediate-immune-tolerance-induced-by-ctla4ig-and-anti-cd154-hematopoietic-stem-cell-transplantation-in-a-sensitized-mouse-model
#8
Qi-Xiang Ye, Lv-Hong Xu, Pei-Jie Shi, Ting Xia, Jian-Pei Fang
Cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig) and anti-cluster of differentiation 154 (anti-CD154) are able to block B7/CD28 and CD40/CD154 co-stimulatory signals in T cells. Additionally, they promote hematopoietic stem cell transplantation (HSCT) in sensitized recipients and are able to induce immune tolerance and complete hematopoietic reconstitution. Indoleamine 2, 3-dioxygenase (IDO) and nitric oxide (NO) have been implicated in T cell immune tolerance. The aim of the present report was to study the in vivo tolerogenic mechanisms by which CTLA4Ig and anti-CD154 induce transplantation survival in mice receiving HSCT...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28960227/tolerogenic-dendritic-cells-induced-by-bd750-ameliorate-proinflammatory-t-cell-responses-and-experimental-autoimmune-encephalitis-in-mice
#9
Yan Zhou, Xiao Leng, Hua Li, Shuxia Yang, Tai Yang, Limei Li, Ying Xiong, Qiang Zou, Yang Liu, Yantang Wang
BD750, a novel JAK3/STAT5 inhibitor, can inhibit T cell proliferation. This study aims to evaluate whether BD750 can induce tolerogenic dendritic cells (tolDC) and their function in experimental autoimmune encephalitis (EAE) in mice. Following BD750 treatment, LPS-induced maturation of DC, allogeneic T cell proliferation, Th1 and Th17 cell functional differentiation, the STAT5 and AKT activation were determined. The effect of tolDC loaded with antigen peptide on the development and severity of EAE and their splenic Th1 and Th17 cell responses were determined...
September 27, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28959261/a-novel-approach-to-reinstating-tolerance-in-experimental-autoimmune-myasthenia-gravis-using-a-targeted-fusion-protein-mcta1-t146
#10
Alessandra Consonni, Sapna Sharma, Karin Schön, Cristina Lebrero-Fernández, Elena Rinaldi, Nils Yngve Lycke, Fulvio Baggi
Reinstating tissue-specific tolerance has attracted much attention as a means to treat autoimmune diseases. However, despite promising results in rodent models of autoimmune diseases, no established tolerogenic therapy is clinically available yet. In the experimental autoimmune myasthenia gravis (EAMG) model several protocols have been reported that induce tolerance against the prime disease-associated antigen, the acetylcholine receptor (AChR) at the neuromuscular junction. Using the whole AChR, the extracellular part or peptides derived from the receptor, investigators have reported variable success with their treatments, though, usually relatively large amounts of antigen has been required...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28950267/detection-of-the-peanut-allergens-ara-h-2-and-ara-h-6-in-human-breast-milk-development-of-2-sensitive-and-specific-sandwich-elisa-assays
#11
Frauke Schocker, Alexandra Scharf, Skadi Kull, Uta Jappe
BACKGROUND: Little is known about breast milk as a vehicle for tolerance development or sensitization to peanuts very early in life. Thus, well-characterized and highly sensitive detection systems for the reliable determination of peanut allergens in breast milk are mandatory. METHODS: For the quantification of the marker allergens Ara h 2 and Ara h 6 in the low nanogram per milliliter range in breast milk samples of a German cohort, sensitive and highly specific sandwich ELISAs were optimized and validated...
September 27, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28946811/impaired-function-of-bone-marrow-mesenchymal-stem-cells-from-immune-thrombocytopenia-patients-in-inducing-regulatory-dc-differentiation-via-the-notch-1-jagged-1-signaling-pathway
#12
Linlin Xu, Haixia Fu, Jiamin Zhang, Feier Feng, Qianming Wang, Xiaolu Zhu, Jing Xue, Chencong Wang, Qi Chen, Xiao Liu, Yazhe Wang, Yazhen Qin, Yuan Kong, Yingjun Chang, Lanping Xu, Kaiyan Liu, Xiaojun Huang, Xiaohui Zhang
Immune thrombocytopenia (ITP) is an autoimmune disease in which dendritic cells (DCs) play a crucial role in the break-down of self-tolerance. Studies have identified the function of mesenchymal stem cells (MSCs) in promoting the development of regulatory DCs (regDCs). Our previous work revealed that MSCs in ITP exerted senescence, apoptosis and impaired immunosuppressive effects on T and B cells. However, it is unclear whether the effects of MSCs on regDC induction are altered in ITP. Our data demonstrated that MSCs in ITP were impaired in inhibiting CD1a+DC and CD14+DC differentiation from CD34+ hematopoietic progenitor cells (CD34+HPCs)...
September 25, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28943274/gene-therapy-induced-antigen-specific-tregs-inhibit-neuro-inflammation-and-reverse-disease-in-a-mouse-model-of-multiple-sclerosis
#13
Geoffrey D Keeler, Sandeep Kumar, Brett Palaschak, Emily L Silverberg, David M Markusic, Noah T Jones, Brad E Hoffman
The devastating neurodegenerative disease multiple sclerosis (MS) could substantially benefit from an adeno-associated virus (AAV) immunotherapy designed to restore a robust and durable antigen-specific tolerance. However, developing a sufficiently potent and lasting immune-regulatory therapy that can intervene in ongoing disease is a major challenge and has thus been elusive. We addressed this problem by developing a highly effective and robust tolerance-inducing in vivo gene therapy. Using a pre-clinical animal model, we designed a liver-targeting gene transfer vector that expresses full-length myelin oligodendrocyte glycoprotein (MOG) in hepatocytes...
September 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28939389/recombinant-allergen-and-peptide-based-approaches-for-allergy-prevention-by-oral-tolerance
#14
REVIEW
Raffaela Campana, Huey-Jy Huang, Raphaela Freidl, Birgit Linhart, Susanne Vrtala, Thomas Wekerle, Alexander Karaulov, Rudolf Valenta
Several studies conducted in animal models for immunologically-mediated hypersensitivity diseases have shown that oral administration of antigens early in life can prevent the development of specific humoral and cellular immune responses and thus hypersensitivity reactions to the respective antigens. Such data were also obtained in models for Immunoglobulin E (IgE)-associated allergy, the most common hypersensitivity disease affecting more than 25% of the population. Based on data obtained in animal models for allergy several clinical intervention studies have been conducted in children to study if oral administration of materials containing allergens or allergen-derived peptides early in life can prevent the subsequent development of allergy...
September 20, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28932226/immunomodulatory-properties-of-coriolus-versicolor-the-role-of-polysaccharopeptide
#15
REVIEW
Mohammad H Saleh, Iran Rashedi, Armand Keating
Traditional uses of herbal medicine have depended mostly on anecdotal evidence for much of history. The increasing application of scientific rigor to the study some of these traditional therapies in recent years has revealed potent bioactivity, notably demonstrated by the 2015 Nobel Prize for the discovery of an antimalarial compound from traditional Chinese herbs. Given the recent successes of immunotherapy and checkpoint blockade, there is a renewed interest in identifying new drugs with immunomodulatory effects...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28930663/the-trem2-apoe-pathway-drives-the-transcriptional-phenotype-of-dysfunctional-microglia-in-neurodegenerative-diseases
#16
Susanne Krasemann, Charlotte Madore, Ron Cialic, Caroline Baufeld, Narghes Calcagno, Rachid El Fatimy, Lien Beckers, Elaine O'Loughlin, Yang Xu, Zain Fanek, David J Greco, Scott T Smith, George Tweet, Zachary Humulock, Tobias Zrzavy, Patricia Conde-Sanroman, Mar Gacias, Zhiping Weng, Hao Chen, Emily Tjon, Fargol Mazaheri, Kristin Hartmann, Asaf Madi, Jason D Ulrich, Markus Glatzel, Anna Worthmann, Joerg Heeren, Bogdan Budnik, Cynthia Lemere, Tsuneya Ikezu, Frank L Heppner, Vladimir Litvak, David M Holtzman, Hans Lassmann, Howard L Weiner, Jordi Ochando, Christian Haass, Oleg Butovsky
Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic β-amyloid (Aβ)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28928446/tumour-derived-pgd2-and-nkp30-b7h6-engagement-drives-an-immunosuppressive-ilc2-mdsc-axis
#17
Sara Trabanelli, Mathieu F Chevalier, Amaia Martinez-Usatorre, Alejandra Gomez-Cadena, Bérengère Salomé, Mariangela Lecciso, Valentina Salvestrini, Grégory Verdeil, Julien Racle, Cristina Papayannidis, Hideaki Morita, Irene Pizzitola, Camille Grandclément, Perrine Bohner, Elena Bruni, Mukul Girotra, Rani Pallavi, Paolo Falvo, Elisabeth Oppliger Leibundgut, Gabriela M Baerlocher, Carmelo Carlo-Stella, Daniela Taurino, Armando Santoro, Orietta Spinelli, Alessandro Rambaldi, Emanuela Giarin, Giuseppe Basso, Cristina Tresoldi, Fabio Ciceri, David Gfeller, Cezmi A Akdis, Luca Mazzarella, Saverio Minucci, Pier Giuseppe Pelicci, Emanuela Marcenaro, Andrew N J McKenzie, Dominique Vanhecke, George Coukos, Domenico Mavilio, Antonio Curti, Laurent Derré, Camilla Jandus
Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28923404/hla-g-coding-region-polymorphism-is-skewed-in-autistic-spectrum-disorders
#18
Franca R Guerini, Elisabetta Bolognesi, Matteo Chiappedi, Enrico Ripamonti, Alessandro Ghezzo, Michela Zanette, Stefano Sotgiu, Maria Martina Mensi, Alessandra Carta, Maria Paola Canevini, Milena Zanzottera, Cristina Agliardi, Andrea S Costa, Umberto Balottin, Mario Clerici
Different isoforms of HLA-G protein are endowed with a differential ability to induce allogenic tolerance during pregnancy. As prenatal immune activation is suggested to play a role in the onset of autistic spectrum disorders (ASD), we evaluated HLA G*01:01-*01:06 allelic polymorphism in a cohort of Italian children affected by ASD (N=111) their mothers (N=81), and their healthy siblings (N=39). DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies; alleles distribution was compared with that of two control groups of Caucasoid couples of multiparous women and their partners from Brazil and Denmark...
September 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28919987/programmed-death-ligand-1-pd-l1-expression-influences-the-immune-tolerogenic-microenvironment-in-antiretroviral-therapy-refractory-kaposi-s-sarcoma-a-pilot-study
#19
Salvinia Mletzko, David J Pinato, Rebecca C Robey, Alessia Dalla Pria, Peter Benson, Nesrina Imami, Mark Bower
Upregulation of programmed death ligand 1 (PD-L1) is a mechanism of immune escape utilized by a variety of tumors. PD-L1 expression in tumor cells or in the surrounding infiltrate correlates with clinical responsiveness to novel therapies targeting the PD-1/PD-L1 immune checkpoint. In the context of HIV-1 infection, Kaposi's sarcoma (KS) is largely responsive to restoration of immunity following combination antiretroviral therapy (cART), but there is a subset that is not. We hypothesized that this subset of cART-refractory KS may utilize the PD-L1 pathway of immune escape...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919171/immunomodulatory-mechanisms-of-mesenchymal-stem-cells-and-their-therapeutic-applications
#20
Don K Lee, Sun U Song
In the recent years, many studies have shown that MSCs must be stimulated by pro-inflammatory cytokines or other immune mediators before they can modulate immune cells in inflamed and damaged tissues. MSCs appear to be involved in inducing several regulatory immune cells, such as Tregs, Bregs, and regulatory NK cells. This new immune milieu created by MSCs may establish a tolerogenic environment that leads to an optimal condition for the treatment of immune diseases. The mechanisms of MSC action to treat immune disorders need to be further investigated in more detail...
September 11, 2017: Cellular Immunology
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