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https://www.readbyqxmd.com/read/28936523/mesoporous-zno-nanocapsules-for-the-induction-of-enhanced-antigen-specific-immunological-responses
#1
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/28935714/profiling-mhc-ii-immunopeptidome-of-blood-stage-malaria-reveals-that-cdc1-control-the-functionality-of-parasite-specific-cd4-t-cells
#2
Marion Draheim, Myriam F Wlodarczyk, Karine Crozat, Jean-Michel Saliou, Tchilabalo Dilezitoko Alayi, Stanislas Tomavo, Ali Hassan, Anna Salvioni, Claudia Demarta-Gatsi, John Sidney, Alessandro Sette, Marc Dalod, Antoine Berry, Olivier Silvie, Nicolas Blanchard
In malaria, CD4 Th1 and T follicular helper (TFH) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins...
September 21, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28935569/constitutive-cd40-signaling-in-dendritic-cells-limits-atherosclerosis-by-provoking-inflammatory-bowel-disease-and-ensuing-cholesterol-malabsorption
#3
Pascal Kusters, Tom Seijkens, Christina Bürger, Bart Legein, Holger Winkels, Marion Gijbels, Christian Barthels, Remy Bennett, Linda Beckers, Dorothee Atzler, Erik Biessen, Thomas Brocker, Christian Weber, Norbert Gerdes, Esther Lutgens
The co-stimulatory molecule CD40 is a major driver of atherosclerosis. It is expressed on a wide variety of cell types including mature dendritic cells (DCs) and is required for optimal T cell activation and expansion. It remains undetermined if and how CD40 on DCs impacts the pathogenesis of atherosclerosis. Here we examined the effects of constitutively active CD40 in DCs on atherosclerosis, using low-density lipoprotein-deficient (Ldlr(-/-)) bone-marrow chimeras that express a transgene containing an engineered latent membrane protein 1 (LMP)/CD40 fusion protein conferring constitutive CD40 signaling under control of the DC-specific CD11c promoter (DC-LMP1/CD40)...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28934241/hla-dr7-and-hla-dq2-transgenic-mouse-strains-tested-as-a-model-system-for-ximelagatran-hepatotoxicity
#4
Hanna Lundgren, Klara Martinsson, Karin Cederbrant, Johan Jirholt, Daniel Mucs, Katja Madeyski-Bengtson, Said Havarinasab, Per Hultman
The oral thrombin inhibitor ximelagatran was withdrawn in the late clinical trial phase because it adversely affected the liver. In approximately 8% of treated patients, drug-induced liver injury (DILI) was expressed as transient alanine transaminase (ALT) elevations. No evidence of DILI had been revealed in the pre-clinical in vivo studies. A whole genome scan study performed on the clinical study material identified a strong genetic association between the major histocompatibility complex alleles for human leucocyte antigens (HLA) (HLA-DR7 and HLA-DQ2) and elevated ALT levels in treated patients...
2017: PloS One
https://www.readbyqxmd.com/read/28931687/a-dna-vaccine-that-targets-hemagglutinin-to-antigen-presenting-cells-protects-mice-against-h7-influenza
#5
Tor Kristian Andersen, Fan Zhou, Rebecca Cox, Bjarne Bogen, Gunnveig Grødeland
Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we have constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1)...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28931654/cancer-immunotherapy-with-recombinant-poliovirus-induces-ifn-dominant-activation-of-dendritic-cells-and-tumor-antigen-specific-ctls
#6
Michael C Brown, Eda K Holl, David Boczkowski, Elena Dobrikova, Mubeen Mosaheb, Vidya Chandramohan, Darell D Bigner, Matthias Gromeier, Smita K Nair
Tumors thrive in an immunosuppressive microenvironment that impedes antitumor innate and adaptive immune responses. Thus, approaches that can overcome immunosuppression and engage antitumor immunity are needed. This study defines the adjuvant and cancer immunotherapy potential of the recombinant poliovirus/rhinovirus chimera PVSRIPO. PVSRIPO is currently in clinical trials against recurrent World Health Organization grade IV malignant glioma, a notoriously treatment-refractory cancer. Cytopathogenic infection of neoplastic cells releases the proteome and exposes pathogen- and damage-associated molecular patterns...
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
#7
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/28930779/inhibition-of-lymphatic-drainage-with-a-self-designed-surgical-approach-prolongs-the-vascularized-skin-allograft-survival-in-rats
#8
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/28929190/mining-the-complex-family-of-protein-tyrosine-phosphatases-for-checkpoint-regulators-in-immunity
#9
Claudia Penafuerte, Luis Alberto Perez-Quintero, Valerie Vinette, Teri Hatzihristidis, Michel L Tremblay
The family of protein tyrosine phosphatases (PTPs) includes 107 genes in humans that are diverse in their structures and expression profiles. The majority are present in immune cells and play various roles in either inhibiting or promoting the duration and amplitude of signaling cascades. Several PTPs, including TC-PTP (PTPN2) and SHP-1 (PTPN6), have been recognized as being crucial for maintaining proper immune response and self-tolerance, and have gained recognition as true immune system checkpoint modulators...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28929188/differential-modulation-of-il-12-family-cytokines-in-autoimmune-islet-graft-failure-in-mice
#10
Feng-Cheng Chou, Heng-Yi Chen, Hsin-Hui Chen, Gu-Jiun Lin, Shih-Hua Lin, Huey-Kang Sytwu
AIMS/HYPOTHESIS: The relative contribution of T helper (Th)1 and Th17 cells in graft rejection is inconclusive, on the basis of evidence provided by different T cell-related cytokine-deficient animal models and graft types. METHODS: We used novel antigen-presenting-cell-specific Il-12p35 (also known as Il12a)-knockout (KO), IL-23p19-knockdown (KD) and IL-27p28-KD strategies to investigate T cell differentiation in islet graft rejection. RESULTS: In vitro dendritic cell-T cell coculture experiments revealed that dendritic cells from Il-12p35-KO and IL-23p19-KD mice showed reduced ability to stimulate IFN-γ and IL-17 production in T cells, respectively...
September 19, 2017: Diabetologia
https://www.readbyqxmd.com/read/28928743/the-toll-for-trafficking-toll-like-receptor-7-delivery-to-the-endosome
#11
REVIEW
Carlene Petes, Natalya Odoardi, Katrina Gee
Toll-like receptor (TLR)-7 is an endosomal innate immune sensor capable of detecting single-stranded ribonucleic acid. TLR7-mediated induction of type I interferon and other inflammatory cytokine production is important in antiviral immune responses. Furthermore, altered TLR7 expression levels are implicated in various autoimmune disorders, indicating a key role for this receptor in modulating inflammation. This review is focused on the regulation of TLR7 expression and localization compared to that of the other endosomal TLRs: TLR3, 8, and 9...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28926543/ontogeny-and-function-of-murine-epidermal-langerhans-cells
#12
REVIEW
Daniel H Kaplan
Langerhans cells (LCs) are epidermis-resident antigen-presenting cells that share a common ontogeny with macrophages but function as dendritic cells (DCs). Their development, recruitment and retention in the epidermis is orchestrated by interactions with keratinocytes through multiple mechanisms. LC and dermal DC subsets often show functional redundancy, but LCs are required for specific types of adaptive immune responses when antigen is concentrated in the epidermis. This Review will focus on those developmental and functional properties that are unique to LCs...
September 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28926189/environmental-peer-pressure-cd4-t-cell-help-in-tolerance-and-transplantation
#13
REVIEW
Dana Tedesco, Arash Grakoui
The liver participates in a multitude of metabolic functions that are critical for sustaining human life. Despite constant encounters with antigenic-rich intestinal blood, oxidative stress and metabolic intermediates, there is no appreciable immune response. Interestingly, patients undergoing orthotopic liver transplantation benefit from a high rate of graft acceptance in comparison to other solid organ transplant recipients. In fact, co-transplantation of a donor liver in tandem with a rejection-prone graft increases the likelihood of graft acceptance...
September 19, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28923936/isolation-of-exosomes-from-whole-blood-by-integrating-acoustics-and-microfluidics
#14
Mengxi Wu, Yingshi Ouyang, Zeyu Wang, Rui Zhang, Po-Hsun Huang, Chuyi Chen, Hui Li, Peng Li, David Quinn, Ming Dao, Subra Suresh, Yoel Sadovsky, Tony Jun Huang
Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosome-based biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contact-free manner...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923858/anti-cd137-suppresses-tumor-growth-by-blocking-reverse-signaling-by-cd137-ligand
#15
Sang W Kang, Sang Chul Lee, So H Park, Juyang Kim, Hyeon H Kim, Hyeon-Woo Lee, Su-Kil Seo, Byoung S Kwon, Hong R Cho, Byungsuk Kwon
CD137 (4-1BB) is a T cell co-stimulatory molecule and agonstic CD137 antibodies are currently being evaluated in clinic as cancer immunotherapy. Recently, it was found that CD137-/- mice or mice injected with agonistic anti-CD137 antibodies exhibit heightened antitumor responses, contrary to expectations based on other knowledge of CD137 function. Here we report findings related to reverse signaling by CD137 ligand (CD137L) in antigen-presenting dendritic cells (DC) in tumors that address these paradoxical results...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923762/translating-basic-research-into-clinical-practice-vitamin-d-in-asthma-mechanisms-of-action-and-considerations-for-clinical-trials
#16
REVIEW
Paul E Pfeffer, Catherine M Hawrylowicz
There is increasing interest in the therapeutic utility of vitamin D in asthma, supported by a significant body of evidence on epidemiological associations between vitamin D insufficiency and worse asthma control. In support of a causal relationship, vitamin D beneficially modulates diverse immunological pathways in heterogeneous asthma endotypes, regulating the actions of lymphocytes, mast cells, antigen-presenting cells and structural cells to dampen excessive inflammatory responses. Allergic asthma is characterised by a failure of immune tolerance, and development of pathological responses to inhaled aeroallergens, and vitamin D has been extensively shown to support immune regulation...
September 15, 2017: Chest
https://www.readbyqxmd.com/read/28922848/aggressive-behavior-in-silent-subtype-iii-pituitary-adenomas-may-depend-on-suppression-of-local-immune-response-a-whole-transcriptome-analysis
#17
Timothy E Richardson, Zhong-Jian Shen, Mohammed Kanchwala, Chao Xing, Alexander Filatenkov, Ping Shang, Samuel Barnett, Zahidur Abedin, James S Malter, Jack M Raisanen, Dennis K Burns, Charles L White, Kimmo J Hatanpaa
Silent subtype III pituitary adenomas (SS-3) are clinically nonfunctional adenomas that are more aggressive in terms of invasion and risk of recurrence than their conventional null cell counterparts. We previously showed that these tumors can be distinguished by immunohistochemistry based on the identification of a markedly enlarged and fragmented Golgi apparatus. To understand the molecular correlates of differential aggressiveness, we performed whole transcriptome sequencing (RNAseq) on 4 SS-3 and 4 conventional null cell adenomas...
October 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28921946/biomimetic-magnetosomes-as-versatile-artificial-antigen-presenting-cells-to-potentiate-t-cell-based-anticancer-therapy
#18
Qianmei Zhang, Wei Wei, Peilin Wang, Liping Zuo, Feng Li, Jin Xu, Xiaobo Xi, Xiaoyong Gao, Guanghui Ma, Hai-Yan Xie
Adoptive T-cell transfer for cancer therapy relies on both effective ex vivo T-cell expansion and in vivo targeting performance. One promising but challenging method for accomplishing this purpose is to construct multifunctional artificial antigen-presenting cells (aAPCs). We herein developed biomimetic magnetosomes as versatile aAPCs, wherein magnetic nanoclusters were coated with azide-engineered leucocyte membranes and then decorated with T-cell stimuli through copper-free click chemistry. These nano aAPCs not only exhibited high performance for antigen-specific cytotoxic T-cell (CTL) expansion and stimulation but also visually and effectively guided reinfused CTLs to tumor tissues through magnetic resonance imaging and magnetic control...
September 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28921472/telomere-damage-response-and-low-grade-inflammation
#19
Lihui Wang, Xianhua Yu, Jun-Ping Liu
Telomeres at the ends of chromosomes safeguard genome integrity and stability in human nucleated cells. However, telomere repeats shed off during cell proliferation and other stress responses. Our recent studies show that telomere attrition induces not only epithelial stem cell senescence but also low-grade inflammation in the lungs. The senescence-associated low-grade inflammation (SALI) is characteristic of alveolar stem cell replicative senescence, increased proinflammatory and anti-inflammatory cytokines, infiltrated immune cells, and spillover effects...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28919706/profile-of-pembrolizumab-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma-design-development-and-place-in-therapy
#20
REVIEW
Sulsal Haque, Mahender Yellu, Jaskirat Randhawa, Nooshin Hashemi-Sadraei
Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance...
2017: Drug Design, Development and Therapy
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