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https://www.readbyqxmd.com/read/28937406/tolerance-in-xenotransplantation
#1
Kazuhiko Yamada, Megan Sykes, David H Sachs
PURPOSE OF REVIEW: This review describes recent progress in tolerance-inducing strategies across xenogeneic immunological barriers as well as the potential benefit of a tolerance strategy for islets and kidney xenotransplantation. RECENT FINDINGS: Using advanced gene editing technologies, xenotransplantation from multitransgenic alpha-1,3-galactosyltransferase knockout pigs has demonstrated marked prolongation of renal xenograft survival, ranging from days to greater than several months for life-supporting kidneys, and more than 2 years in a heterotopic nonlife-supporting cardiac xenograft model...
September 20, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28936778/preferential-reduction-of-circulating-innate-lymphoid-cells-type-2-in-patients-with-common-variable-immunodeficiency-with-secondary-complications-is-part-of-a-broader-immune-dysregulation
#2
David Friedmann, Baerbel Keller, Ina Harder, Jonas Schupp, Yakup Tanriver, Susanne Unger, Klaus Warnatz
PURPOSE: Over a third of patients with common variable immunodeficiency (CVID) suffer from secondary complications like inflammatory organ disease, autoimmune manifestations, or lymphoproliferation contributing to increased morbidity and mortality in affected patients. Innate lymphoid cells (ILCs) have emerging roles in setting the milieu for physiological, but also pathological, immune responses and inflammation. We therefore sought to correlate the recently identified disturbed homeostasis of ILCs with alterations of the adaptive immune system in complex CVID patients (CVIDc)...
September 21, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28936523/mesoporous-zno-nanocapsules-for-the-induction-of-enhanced-antigen-specific-immunological-responses
#3
Sumbul Afroz, Himadri Medhi, Somedutta Maity, Gillipsie Minhas, Srikanth Battu, Jeevan Giddaluru, Koushi Kumar, Pradip Paik, Nooruddin Khan
The application of nanotechnology in vaccinology has fuelled rapid advancement towards the design and development of nanovaccines. Nanoparticles have been found to enhance vaccine efficacy through the spatiotemporal orchestration of antigen delivery to secondary lymphoid organs and antigen-presentation by Antigen Presenting Cells (APCs) synchronized with stimulation of innate and adaptive immune responses. Metal based nanoparticles (MNPs) have been extensively engineered for the generation of nanovaccines owing to their intrinsic adjuvant-like properties and immunomodulatory functions...
September 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28936212/how-viruses-contribute-to-the-pathogenesis-of-hemophagocytic-lymphohistiocytosis
#4
Ellen Brisse, Carine H Wouters, Graciela Andrei, Patrick Matthys
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, hyperinflammatory syndrome, characterized by the uncontrolled activation of macrophages and T cells, eliciting key symptoms such as persistent fever, hepatosplenomegaly, pancytopenia, hemophagocytosis, hyperferritinemia, and coagulopathy. Viral infections are frequently implicated in the onset of active HLH episodes, both in primary, genetic HLH as in the secondary, acquired form. Infections with herpesviruses such as Epstein-Barr virus and cytomegalovirus are the most common...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28936204/modulatory-influence-of-segmented-filamentous-bacteria-on-transcriptomic-response-of-gnotobiotic-mice-exposed-to-tcdd
#5
Robert D Stedtfeld, Benli Chai, Robert B Crawford, Tiffany M Stedtfeld, Maggie R Williams, Shao Xiangwen, Tomomi Kuwahara, James R Cole, Norbert E Kaminski, James M Tiedje, Syed A Hashsham
Environmental toxicants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AhR), are known to induce host toxicity and structural shifts in the gut microbiota. Key bacterial populations with similar or opposing functional responses to AhR ligand exposure may potentially help regulate expression of genes associated with immune dysfunction. To examine this question and the mechanisms for AhR ligand-induced bacterial shifts, C57BL/6 gnotobiotic mice were colonized with and without segmented filamentous bacteria (SFB) - an immune activator...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28935974/membrane-particles-generated-from-mesenchymal-stromal-cells-modulate-immune-responses-by-selective-targeting-of-pro-inflammatory-monocytes
#6
Fabiany da C Gonçalves, Franka Luk, Sander S Korevaar, Rachid Bouzid, Ana H Paz, Carmen López-Iglesias, Carla C Baan, Ana Merino, Martin J Hoogduijn
Mesenchymal stromal cells (MSC) are a promising therapy for immunological disorders. However, culture expanded MSC are large and get trapped in the capillary networks of the lungs after intravenous infusion, where they have a short survival time. Hypothetically, living cells are a risk for tumor formation. To reduce risks associated with MSC infusion and improve the distribution in the body, we generated membrane particles (MP) of MSC and MSC stimulated with IFN-γ (MPγ). Tracking analysis and electron microscopy indicated that the average size of MP was 120 nm, and they showed a round shape...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935847/cd56bright-nk-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-gvhd-cbmtg-randomized-0601-study-results
#7
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Silvy Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeen Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephen Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
September 21, 2017: Haematologica
https://www.readbyqxmd.com/read/28934427/immunologic-profiling-of-human-metapneumovirus-for-the-development-of-targeted-immunotherapy
#8
Ifigeneia Tzannou, Sarah K Nicholas, Premal Lulla, Paibel I Aguayo-Hiraldo, Anisha Misra, Caridad A Martinez, Annette A Machado, Jordan S Orange, Pedro A Piedra, Juan F Vera, Ann M Leen
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28932628/a-novel-in-silico-framework-to-improve-mhc-i-epitopes-and-break-the-tolerance-to-melanoma
#9
Cristian Capasso, Aniket Magarkar, Victor Cervera-Carascon, Manlio Fusciello, Sara Feola, Martin Muller, Mariangela Garofalo, Lukasz Kuryk, Siri Tähtinen, Lucio Pastore, Alex Bunker, Vincenzo Cerullo
Tolerance toward tumor antigens, which are shared by normal tissues, have often limited the efficacy of cancer vaccines. However, wild type epitopes can be tweaked to activate cross-reactive T-cell clones, resulting in antitumor activity. The design of these analogs (i.e., heteroclitic peptides) can be difficult and time-consuming since no automated in silico tools are available. Hereby we describe the development of an in silico framework to improve the selection of heteroclitic peptides. The Epitope Discovery and Improvement System (EDIS) was first validated by studying the model antigen SIINFEKL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931689/vaccination-with-recombinant-parainfluenza-virus-5-expressing-neuraminidase-protects-against-homologous-and-heterologous-influenza-virus-challenge
#10
Alaina J Mooney, Jon D Gabbard, Zhuo Li, Daniel A Dlugolenski, Scott K Johnson, Ralph A Tripp, Biao He, S Mark Tompkins
Seasonal human influenza virus continues to cause morbidity and mortality annually, and highly pathogenic avian influenza (HPAI) along with other emerging influenzas continue to pose pandemic threats. Vaccination is considered the most effective measure for controlling influenza; however, current strategies rely on a precise vaccine match with currently circulating virus strains for efficacy, requiring constant surveillance and regular development of matched vaccines. Current vaccines focus on eliciting specific antibody responses against the hemagglutinin (HA) surface glycoprotein; however, the diversity of HAs across species and antigenic drift of circulating strains enables evasion of virus-inhibiting antibody responses, resulting in vaccine failure...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#11
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28931462/paradoxical-development-of-polymyositis-like-autoimmunity-through-augmented-expression-of-autoimmune-regulator-aire
#12
Hitoshi Nishijima, Tatsuya Kajimoto, Yoshiki Matsuoka, Yasuhiro Mouri, Junko Morimoto, Minoru Matsumoto, Hiroshi Kawano, Yasuhiko Nishioka, Hisanori Uehara, Keisuke Izumi, Koichi Tsuneyama, Il-Mi Okazaki, Taku Okazaki, Kazuyoshi Hosomichi, Ayako Shiraki, Makoto Shibutani, Kunitoshi Mitsumori, Mitsuru Matsumoto
Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs...
September 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28930796/navigating-t-cell-immunometabolism-in-transplantation
#13
Naoki Tanimine, Laurence A Turka, Bhavana Priyadharshini
Recently, a new discipline termed "immunometabolism" has transformed the field of immunology. It encompasses the study of the intrinsic metabolic pathways of different immune subsets and their impact on cellular fate and function. For instance, broadly speaking, pro-inflammatory cells depend upon glycolysis and glutamine oxidation while cells involved in anti-inflammatory response such as Foxp3+ regulatory T cells (Tregs) utilize predominantly fatty acid oxidation. However, while a useful paradigm, this actually is a reductionist view and the engagement of these metabolic pathways is not mutually exclusive between these subsets...
September 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28930779/inhibition-of-lymphatic-drainage-with-a-self-designed-surgical-approach-prolongs-the-vascularized-skin-allograft-survival-in-rats
#14
Jiaomiao Pei, Yang Li, Chen Chen, Xi Zhang, Shiping Wang, Yajuan Song, Bei Liu, Yingjun Su, Shuzhong Guo
Vascularized composite allotransplantation (VCA) is an emerging treatment for significant tissue defects. However, VCAs usually consist of multiple highly antigenic skin tissues. Previous studies have shown that the lymphatic system in skin plays important roles in the initiation of immune responses during acute rejection, by transporting T cells and antigen-presenting dendritic cells to regional lymph nodes. Therefore, we designed a new surgical treatment to inhibit lymphatic drainage of skin allografts and investigated whether this approach could promote the survival of allografts and suppress immunological events after transplantation...
September 19, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28930556/osteoimmunology-the-nexus-between-bone-and-immune-system
#15
Hamid Y Dar, Zaffar Azam, Rajaneesh Anupam, Rajesh K Mondal, Rupesh K Srivastava
Osteoimmunology is an interdisciplinary research field which combines the existing fields of osteology (bone biology) and immunology under one umbrella. The observation that contributed enormously to the emergence of osteoimmunology as an independent field of investigation was the enhanced bone loss in various inflammatory bone diseases such as rheumatoid arthritis, osteoporosis and periodontitis. T helper cells (Th1, Th2, Treg and Th17) along with various other immune cells (B cells, DC, macrophages etc.) are actively involved in bone homeostasis...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930287/exposure-to-human-alveolar-lining-fluid-enhances-mycobacterium-bovis-bcg-vaccine-efficacy-against-mycobacterium-tuberculosis-infection-in-a-cd8-t-cell-dependent-manner
#16
J I Moliva, A P Hossfeld, C H Canan, V Dwivedi, M D Wewers, G Beamer, J Turner, J B Torrelles
Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M...
September 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28930286/molecular-and-cellular-signatures-underlying-superior-immunity-against-bordetella-pertussis-upon-pulmonary-vaccination
#17
R Hm Raeven, J Brummelman, J LA Pennings, L van der Maas, K Helm, W Tilstra, A van der Ark, A Sloots, P van der Ley, W van Eden, W Jiskoot, E van Riet, C Acm van Els, G Fa Kersten, W Gh Han, B Metz
Mucosal immunity is often required for protection against respiratory pathogens but the underlying cellular and molecular mechanisms of induction remain poorly understood. Here, systems vaccinology was used to identify immune signatures after pulmonary or subcutaneous immunization of mice with pertussis outer membrane vesicles. Pulmonary immunization led to improved protection, exclusively induced mucosal immunoglobulin A (IgA) and T helper type 17 (Th17) responses, and in addition evoked elevated systemic immunoglobulin G (IgG) antibody levels, IgG-producing plasma cells, memory B cells, and Th17 cells...
September 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28930285/interleukin-17a-negatively-regulates-lymphangiogenesis-in-t-helper-17-cell-mediated-inflammation
#18
H J Park, C M Yuk, K Shin, S-H Lee
During inflammation lymphatic vessels (LVs) are enlarged and their density is increased to facilitate the migration of activated immune cells and antigens. However, after antigen clearance, the expanded LVs shrink to maintain homeostasis. Here we show that interleukin (IL)-17A, secreted from T helper type 17 (TH17) cells, is a negative regulator of lymphangiogenesis during the resolution phase of TH17-mediated immune responses. Moreover, IL-17A suppresses the expression of major lymphatic markers in lymphatic endothelial cells and decreases in vitro LV formation...
September 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28928888/potential-roles-of-peripheral-dopamine-in-tumor-immunity
#19
REVIEW
Xiang Zhang, Qiaofei Liu, Quan Liao, Yupei Zhao
Recent years, immunotherapy has turned out to be a promising strategy against tumors. Peripheral dopamine (DA) has important roles in immune system among tumor patients. Accumulated reports demonstrate variable expression and distribution of DA receptors (DRs) in diverse immune cells. Interestingly, peripheral DA also involves in tumor progression and it exerts anticancer effects on immunomodulation, which includes inflammasomes in cancer, function of immune effector cells, such as T lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and natural killer (NK) cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928833/disrupted-fibroblastic-reticular-cells-and-interleukin-7-expression-in-tumor-draining-lymph-nodes
#20
Jianbao Gao, Lintao Zhao, Lina Liu, Yang Yang, Bo Guo, Bo Zhu
The immune system of patients with cancer is usually in an inhibitory state. Lymph node (LN) draining of pathological sites provides a suitable microenvironment where adaptive immune responses mainly occur. However, the microenvironment in the tumor draining lymph nodes (TDLNs) of patients with cancer appears to be in favor of tolerance. The effects of tumor cells on TDLNs have not been elaborated clearly. The present results have indicated that tumor cells may directly affect TDLNs by decreasing the fibroblastic reticular cell population that led to less interleukin-7 secretion...
September 2017: Oncology Letters
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