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https://www.readbyqxmd.com/read/29786071/dopamine-d2-receptor-restricts-astrocytic-nlrp3-inflammasome-activation-via-enhancing-the-interaction-of-%C3%AE-arrestin2-and-nlrp3
#1
Jialei Zhu, Zhaoli Hu, Xiaojuan Han, Dongshuo Wang, Qingling Jiang, Jianhua Ding, Ming Xiao, Cong Wang, Ming Lu, Gang Hu
Astrocytes are involved in the neuroinflammation of neurodegenerative diseases, such as Parkinson's disease (PD). Among the numerous inflammatory cytokines, interleukin-1β (IL-1β) produced by astrocytic Nod-like receptor protein (NLRP) inflammasome is crucial in the pathogenesis of PD. β-arrestin2-mediated dopamine D2 receptor (Drd2) signal transduction has been regarded as a potential anti-inflammatory target. Our previous study revealed that astrocytic Drd2 suppresses neuroinflammation in the central nervous system...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29781952/optimizing-temperature-and-oxygen-supports-long-term-culture-of-human-islets
#2
Hirotake Komatsu, Jeffrey Rawson, Leonard Medrano, Colin A Cook, Alyssa Barriga, Nelson Gonzalez, Mayra Salgado, Keiko Omori, Fouad Kandeel, Yu-Chong Tai, Yoko Mullen
BACKGROUND: Islet transplantation is a promising treatment for type-1 diabetes; however, donor shortage is a concern. Even when a pancreas is available, low islet yield limits the success of transplantation. Islet culture enables pooling of multiple low-yield isolations into an effective islet mass, but isolated islets rapidly deteriorate under conventional culture conditions. Oxygen depletion in the islet core, which leads to central necrosis and volume loss, is one of the major reasons for this deterioration...
May 16, 2018: Transplantation
https://www.readbyqxmd.com/read/29774025/co-stimulation-impaired-bone-marrow-derived-dendritic-cells-prevent-dextran-sodium-sulfate-induced-colitis-in-mice
#3
Carl Engman, Yesica Garciafigueroa, Brett Eugene Phillips, Massimo Trucco, Nick Giannoukakis
Dendritic cells (DC) are important in the onset and severity of inflammatory bowel disease (IBD). Tolerogenic DC induce T-cells to become therapeutic Foxp3+ regulatory T-cells (Tregs). We therefore asked if experimental IBD could be prevented by administration of bone marrow-derived DC generated under conventional GM-CSF/IL-4 conditions but in the presence of a mixture of antisense DNA oligonucleotides targeting the primary transcripts of CD40, CD80, and CD86. These cell products (which we call AS-ODN BM-DC) have demonstrated tolerogenic activity in preventing type 1 diabetes and preserving beta cell mass in new-onset type 1 diabetes in the NOD mouse strain, in earlier studies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769244/a-cs1-nkg2d-bispecific-antibody-collectively-activates-cytolytic-immune-cells-against-multiple-myeloma
#4
Wing Keung Chan, Siwen Kang, Youssef Youssef, Erin N Glankler, Emma R Barrett, Alex M Carter, Elshafa H Ahmed, Aman Prasad, Luxi Chen, Jianying Zhang, Don M Benson, Michael A Caligiuri, Jianhua Yu
Multiple myeloma (MM) is an incurable hematological malignancy of plasma cells with an estimated 30,000 new cases diagnosed each year in the United States, signifying the need for new therapeutic approaches. We hypothesized that targeting MM using a bispecific antibody (biAb) to simultaneously engage both innate and adaptive cytolytic immune cells could present potent antitumor activity. We engineered a biAb by fusing an anti-CS1 single chain variable fragment (scFv) and an anti-NKG2D scFv (CS1-NKG2D biAb)...
May 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29760694/dissemination-of-orientia-tsutsugamushi-a-causative-agent-of-scrub-typhus-and-immunological-responses-in-the-humanized-draga-mouse
#5
Le Jiang, Erin K Morris, Rodrigo Aguilera-Olvera, Zhiwen Zhang, Teik-Chye Chan, Soumya Shashikumar, Chien-Chung Chao, Sofia A Casares, Wei-Mei Ching
Scrub typhus is caused by Orientia tsutsugamushi , an obligated intracellular bacterium that affects over one million people per year. Several mouse models have been used to study its pathogenesis, disease immunology, and for testing vaccine candidates. However, due to the intrinsic differences between the immune systems in mouse and human, these mouse models could not faithfully mimic the pathology and immunological responses developed by human patients, limiting their value in both basic and translational studies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29757216/sphingosine-1-phosphate-receptor-1-is-involved-in-non-obese-diabetic-mouse-thymocyte-migration-disorders
#6
Julia P Lemos, Salete Smaniotto, Carolina V Messias, Otacilio C Moreira, Vinicius Cotta-de-Almeida, Mireille Dardenne, Wilson Savino, Daniella A Mendes-da-Cruz
NOD (non-obese diabetic) mice spontaneously develop type 1 diabetes following T cell-dependent destruction of pancreatic β cells. Several alterations are observed in the NOD thymus, including the presence of giant perivascular spaces (PVS) filled with single-positive (SP) CD4⁺ and CD8⁺ T cells that accumulate in the organ. These cells have a decreased expression of membrane CD49e (the α5 integrin chain of the fibronectin receptor VLA-5 (very late antigen-5). Herein, we observed lower sphingosine-1-phosphate receptor 1 (S1P1) expression in NOD mouse thymocytes when compared with controls, mainly in the mature SP CD4⁺CD62Lhi and CD8⁺CD62Lhi subpopulations bearing the CD49e− phenotype...
May 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29750331/salivary-gland-protective-regulatory-t-cell-dysfunction-underlies-female-specific-sialadenitis-in-the-nonobese-diabetic-mouse-model-of-sj%C3%A3-gren-syndrome
#7
Jennifer Y Barr, Xiaofang Wang, Portia A Kreiger, Scott M Lieberman
Immune cell-mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female nonobese diabetic (NOD) mice develop spontaneous salivary gland autoimmunity. However, in both humans and mice it is unclear what factors contribute to the initial immune infiltration of the salivary glands. Here, we used an adoptive transfer model of Sjögren syndrome to determine if female mice harbor a sex-specific defect in salivary gland-protective regulatory T (Treg) cells...
May 11, 2018: Immunology
https://www.readbyqxmd.com/read/29743205/preclinical-development-of-a-bispecific-antibody-that-safely-and-effectively-targets-cd19-and-cd47-for-the-treatment-of-b-cell-lymphoma-and-leukemia
#8
Vanessa Buatois, Zoë Johnson, Susana Salgado-Pires, Anne Papaïoannou, Eric Hatterer, Xavier Chauchet, Françoise Richard, Leticia Barba, Bruno Daubeuf, Laura Cons, Lucile Broyer, Matilde D'Asaro, Thomas Matthes, Simon LeGallou, Thierry Fest, Karin Tarte, Robert K Clarke Hinojosa, Eulàlia Genescà Ferrer, José María Ribera, Aditi Dey, Katharine Bailey, Adele K Fielding, Linda Eissenberg, Julie Ritchey, Michael Rettig, John F DiPersio, Marie H Kosco-Vilbois, Krzysztof Masternak, Nicolas Fischer, Limin Shang, Walter G Ferlin
CD47, a ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often up-regulated by hematological and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to co-engage CD47 and CD19 selectively on B cells...
May 9, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29743179/a-cd19-cd3-bispecific-antibody-for-effective-immunotherapy-of-chronic-lymphocytic-leukemia-in-the-ibrutinib-era
#9
Hannah R Robinson, Junpeng Qi, Erika M Cook, Cydney Nichols, Eman L Dadashian, Chingiz Underbayev, Sarah E M Herman, Nakhle S Saba, Keyvan Keyvanfar, Clare Sun, Inhye E Ahn, Sivasubramanian Baskar, Christoph Rader, Adrian Wiestner
The Bruton's tyrosine kinase inhibitor ibrutinib induces high rates of clinical response in chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments to deepen response and to overcome drug resistance. Blinatumomab, a CD19/CD3 bispecific antibody (bsAb) designed in the BiTE® format, is FDA approved for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Due to its short half-life of 2.1 hours, blinatumomab requires continuous intravenous dosing for efficacy...
May 9, 2018: Blood
https://www.readbyqxmd.com/read/29742113/paquinimod-prevents-development-of-diabetes-in-the-non-obese-diabetic-nod-mouse
#10
Sahar Tahvili, Marie Törngren, Dan Holmberg, Tomas Leanderson, Fredrik Ivars
Quinoline-3-carboxamides (Q compounds) are immunomodulatory compounds that have shown efficacy both in autoimmune disease and cancer. We have in here investigated the impact of one such compound, paquinimod, on the development of diabetes in the NOD mouse model for type I diabetes (T1D). In cohorts of NOD mice treated with paquinimod between weeks 10 to 20 of age and followed up until 40 weeks of age, we observed dose-dependent reduction in incidence of disease as well as delayed onset of disease. Further, in contrast to untreated controls, the majority of NOD mice treated from 15 weeks of age did not develop diabetes at 30 weeks of age...
2018: PloS One
https://www.readbyqxmd.com/read/29736173/inhibitory-effects-of-ipsc-mscs-and-their-extracellular-vesicles-on-the-onset-of-sialadenitis-in-a-mouse-model-of-sj%C3%A3-gren-s-syndrome
#11
Bo Hai, Taeko Shigemoto-Kuroda, Qingguo Zhao, Ryang Hwa Lee, Fei Liu
No effective treatment for Sjögren's syndrome (SS), a chronic autoimmune disease affecting mainly salivary and lacrimal glands, is available now. Systemic infusion of allogeneic mesenchymal stem cells (MSCs) isolated from tissues such as bone marrow (BM) alleviated SS in mouse models and a small clinical trial, but further research and application of this MSC therapy were hindered by limited expandability, significant donor variations, and safety concerns of tissue-derived MSCs. To circumvent these issues, we derived MSCs from human iPSCs using an optimized protocol that can be easily scaled up to produce a huge amount of standardized MSCs...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29725337/humanized-mice-engrafted-with-human-hsc-only-or-hsc-and-thymus-support-comparable-hiv-1-replication-immunopathology-and-responses-to-art-and-immune-therapy
#12
Liang Cheng, Jianping Ma, Guangming Li, Lishan Su
Immunodeficient mice reconstituted with human immune tissues and cells (humanized mice) are relevant and robust models for the study of HIV-1 infection, immunopathogenesis, and therapy. In this study, we performed a comprehensive comparison of human immune reconstitution and HIV-1 infection, immunopathogenesis and therapy between immunodeficient NOD/Rag2-/- /γc -/- (NRG) mice transplanted with human HSCs (NRG-hu HSC) and mice transplanted with HSCs and thymus fragments (NRG-hu Thy/HSC) from the same donors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29712852/revealing-the-specificity-of-regulatory-t-cells-in-murine-autoimmune-diabetes
#13
Allyson Spence, Whitney Purtha, Janice Tam, Shen Dong, Youmin Kim, Chia-Hsin Ju, Teague Sterling, Maki Nakayama, William H Robinson, Jeffrey A Bluestone, Mark S Anderson, Qizhi Tang
Regulatory T cells (Tregs) control organ-specific autoimmunity in a tissue antigen-specific manner, yet little is known about their specificity in a natural repertoire. In this study, we used the nonobese diabetic (NOD) mouse model of autoimmune diabetes to investigate the antigen specificity of Tregs present in the inflamed tissue, the islets of Langerhans. Compared with Tregs present in spleen and lymph node, Tregs in the islets showed evidence of antigen stimulation that correlated with higher proliferation and expression of activation markers CD103, ICOS, and TIGIT...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29712574/durable-regression-of-medulloblastoma-after-regional-and-intravenous-delivery-of-anti-her2-chimeric-antigen-receptor-t-cells
#14
Anandani Nellan, Christopher Rota, Robbie Majzner, Cynthia M Lester-McCully, Andrea M Griesinger, Jean M Mulcahy Levy, Nicholas K Foreman, Katherine E Warren, Daniel W Lee
BACKGROUND: Standard-of-care therapies for treating pediatric medulloblastoma have long-term side effects, even in children who are cured. One emerging modality of cancer therapy that could be equally effective without such side effects would be chimeric antigen receptor (CAR) T cells. Knowing that human epidermal growth factor receptor 2 (HER2) is overexpressed in many medulloblastomas and has been used as a CAR T target before, we sought to evaluate the efficacy of more sophisticated anti-HER2 CAR T cells, as well as the feasibility and efficacy of different routes of delivering these cells, for the treatment of pediatric medulloblastoma...
April 30, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29707204/loss-of-zbtb32-in-nod-mice-does-not-significantly-alter-t-cell-responses
#15
William D Coley, Yongge Zhao, Charles J Benck, Yi Liu, Chie Hotta-Iwamura, M Jubayer Rahman, Kristin V Tarbell
Background : We previously identified the transcriptional regulator Zbtb32 as a factor that can promote T cell tolerance in the Non-Obese Diabetic (NOD) mouse, a model of Type 1 diabetes. Antigen targeted to DCIR2 + dendritic cells (DCs) in vivo inhibited both diabetes and effector T cell expansion in NOD mice. Furthermore, Zbtb32 was preferentially induced in autoreactive CD4 T cells stimulated by these tolerogenic DCIR2 + DCs, and overexpression of Zbtb32 in islet-specific T cells inhibited the diabetes development by limiting T cell proliferation and cytokine production...
2018: F1000Research
https://www.readbyqxmd.com/read/29705656/humanization-of-bone-and-bone-marrow-in-an-orthotopic-site-reveals-new-potential-therapeutic-targets-in-osteosarcoma
#16
Ferdinand Wagner, Boris M Holzapfel, Jacqui A McGovern, Abbas Shafiee, Jeremy G Baldwin, Laure C Martine, Christoph A Lahr, Felix M Wunner, Thor Friis, Onur Bas, Melanie Boxberg, Peter M Prodinger, Ali Shokoohmand, Davide Moi, Roberta Mazzieri, Daniela Loessner, Dietmar W Hutmacher
BACKGROUND: Existing preclinical murine models often fail to predict effects of anti-cancer drugs. In order to minimize interspecies-differences between murine hosts and human bone tumors of in vivo xenograft platforms, we tissue-engineered a novel orthotopic humanized bone model. METHODS: Orthotopic humanized tissue engineered bone constructs (ohTEBC) were fabricated by 3D printing of medical-grade polycaprolactone scaffolds, which were seeded with human osteoblasts and embedded within polyethylene glycol-based hydrogels containing human umbilical vein endothelial cells (HUVECs)...
April 16, 2018: Biomaterials
https://www.readbyqxmd.com/read/29684359/the-g-protein-coupled-receptor-alx-fpr2-regulates-adaptive-immune-responses-in-mouse-submandibular-glands
#17
Ching-Shuen Wang, Olga J Baker
ALX/FPR2 is a G-protein-coupled receptor that has multiple binding partners, including the endogenous lipid mediators resolvin D1 (RvD1), lipoxin A4 (LXA4 ), and the Ca2+ -dependent phospholipid-binding protein Annexin A1. Previous studies demonstrated that RvD1 activates ALX/FPR2 to resolve salivary gland inflammation in the NOD/ShiLtJ mouse model for Sjögren's syndrome. Moreover, mice lacking the ALX/FPR2 display an exacerbated salivary gland inflammation in response to lipopolysaccharide. Additionally, activation of ALX/FPR2 has been shown to be important for regulating antibody production in B cells...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29680668/anti-il-7-receptor-%C3%AE-treatment-ameliorates-newly-established-sj%C3%A3-gren-s-like-exocrinopathy-in-non-obese-diabetic-mice
#18
Jing Zhou, Qing Yu
The levels of interleukin (IL)-7 and its receptor are elevated in the salivary glands of patients with Sjögren's syndrome (SS). Our previous study indicates that IL-7 plays a critical pathogenic role in the development and onset of SS in a mouse model of this disease. The present study aims at determining whether IL-7 also plays a role in sustaining SS pathologies after the disease onset, by using the non-obese diabetic (NOD) model. Intraperitoneal administration of a blocking antibody against the IL-7 receptor α chain (IL-7Rα) to female NOD mice aged 10 weeks, which exhibited newly onset clinical SS, for the duration of 3 weeks significantly ameliorated characteristic SS pathologies including hyposalivation and leukocyte infiltration of the submandibular glands (SMGs)...
April 19, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29675931/efficacy-studies-of-sclerotium-rolfsii-lectin-on-breast-cancer-using-nod-scid-mouse-model
#19
Prajna Hegde, Jagadeesh Narasimhappagari, Bale M Swamy, Shashikala R Inamdar
Expression of altered glycans like TF, Tn and sTn antigens has been observed in a number of carcinomas which are targeted in cancer therapy. Sclerotium rolfsii lectin (SRL) is known to recognize TF and its substituted forms. Clinical potential of SRL has been demonstrated by studying its interaction with different types of cancer cells. Here we report, in vitro studies of SRL on breast cancer MDA-MB-468 cells and in vivo studies with MCF-7 xenografts. In vitro growth inhibitory studies of SRL on metastatic triple negative breast cancer MDA-MB-468 cells was performed by MTT assay, flow cytometry, adhesion and CAM assay...
April 20, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29675353/magnetic-particle-imaging-of-islet-transplantation-in-the-liver-and-under-the-kidney-capsule-in-mouse-models
#20
Ping Wang, Patrick W Goodwill, Prachi Pandit, Jeff Gaudet, Alana Ross, Junfeng Wang, Elaine Yu, Daniel W Hensley, Timothy C Doyle, Christopher H Contag, Steven Conolly, Anna Moore
Background: Islet transplantation (Tx) represents the most promising therapy to restore normoglycemia in type 1 diabetes (T1D) patients to date. As significant islet loss has been observed after the procedure, there is an urgent need for developing strategies for monitoring transplanted islet grafts. In this report we describe for the first time the application of magnetic particle imaging (MPI) for monitoring transplanted islets in the liver and under the kidney capsule in experimental animals...
March 2018: Quantitative Imaging in Medicine and Surgery
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