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https://www.readbyqxmd.com/read/29228214/oestrogen-receptor-%C3%AE-ligand-acts-on-cd11c-cells-to-mediate-protection-in-experimental-autoimmune-encephalomyelitis
#1
Roy Y Kim, Darian Mangu, Alexandria S Hoffman, Rojan Kovash, Eunice Jung, Noriko Itoh, Rhonda Voskuhl
Oestrogen treatments are neuroprotective in a variety of neurodegenerative disease models. Selective oestrogen receptor modifiers are needed to optimize beneficial effects while minimizing adverse effects to achieve neuroprotection in chronic diseases. Oestrogen receptor beta (ERβ) ligands are potential candidates. In the multiple sclerosis model chronic experimental autoimmune encephalomyelitis, ERβ-ligand treatment is neuroprotective, but mechanisms underlying this neuroprotection remain unclear. Specifically, whether there are direct effects of ERβ-ligand on CD11c+ microglia, myeloid dendritic cells or macrophages in vivo during disease is unknown...
December 8, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29228157/gut-epithelial-vitamin-d-receptor-regulates-microbiota-dependent-mucosal-inflammation-by-suppressing-intestinal-epithelial-cell-apoptosis
#2
Lei He, Tianjing Liu, Yongyan Shi, Feng Tian, Huiyuan Hu, Dilip K Deb, Yinyin Chen, Marc Bissonnette, Yan Chun Li
Recent studies show that colonic vitamin D receptor (VDR) signaling protects the mucosal epithelial barrier and suppresses colonic inflammation, but the underlying molecular mechanism remains to be fully understood. To investigate the implication of colonic VDR down-regulation seen in patients with inflammatory bowel disease, we assessed the effect of gut epithelial VDR deletion on colonic inflammatory responses in an experimental colitis model. In 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model, mice carrying VDR deletion in gut epithelial cells (VDRf/f;Villin-Cre or VDRΔIEC) or in colonic epithelial cells (VDRf/f;CDX2-Cre or VDRΔCEC) developed more severe clinical colitis than VDRf/f control mice, characterized by more robust TH1 and TH17 responses, with greater increases in mucosal IFN-γ+, IL-17+ and IFN-γ+IL-17+ T cells...
December 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/29228015/development-of-an-iron-selective-antioxidant-probe-with-protective-effects-on-neuronal-function
#3
Olimpo García-Beltrán, Natalia P Mena, Pabla Aguirre, Germán Barriga-González, Antonio Galdámez, Edgar Nagles, Tatiana Adasme, Cecilia Hidalgo, Marco T Núñez
Iron accumulation, oxidative stress and calcium signaling dysregulation are common pathognomonic signs of several neurodegenerative diseases, including Parkinson´s and Alzheimer's diseases, Friedreich ataxia and Huntington's disease. Given their therapeutic potential, the identification of multifunctional compounds that suppress these damaging features is highly desirable. Here, we report the synthesis and characterization of N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetamide, named CT51, which exhibited potent free radical neutralizing activity both in vitro and in cells...
2017: PloS One
https://www.readbyqxmd.com/read/29227213/productive-common-light-chain-libraries-yield-diverse-panels-of-high-affinity-bispecific-antibodies
#4
Thomas Van Blarcom, Kevin Lindquist, Zea Melton, Wai Ling Cheung, Chris Wagstrom, Dan McDonough, Cendy Valle Oseguera, Sheng Ding, Andrea Rossi, Shobha Potluri, Purnima Sundar, Steven Pitts, Marina Sirota, Meri Galindo Casas, Yu Yan, Jeffrey Jones, Zygy Roe-Zurz, Surabhi Srivatsa Srinivasan, Wenwu Zhai, Jaume Pons, Arvind Rajpal, Javier Chaparro-Riggers
The commercial success of bispecific antibodies generally has been hindered by the complexities associated with generating appropriate molecules for both research scale and large scale manufacturing purposes. Bispecific IgG (BsIgG) based on two antibodies that use an identical common light chain can be combined with a minimal set of Fc mutations to drive heavy chain heterodimerization in order to address these challenges. However, the facile generation of common light chain antibodies with properties similar to traditional monoclonal antibodies has not been demonstrated and they have only been used sparingly...
December 11, 2017: MAbs
https://www.readbyqxmd.com/read/29226797/axicabtagene-ciloleucel-car-t-cell-therapy-in-refractory-large-b-cell-lymphoma
#5
Sattva S Neelapu, Frederick L Locke, Nancy L Bartlett, Lazaros J Lekakis, David B Miklos, Caron A Jacobson, Ira Braunschweig, Olalekan O Oluwole, Tanya Siddiqi, Yi Lin, John M Timmerman, Patrick J Stiff, Jonathan W Friedberg, Ian W Flinn, Andre Goy, Brian T Hill, Mitchell R Smith, Abhinav Deol, Umar Farooq, Peter McSweeney, Javier Munoz, Irit Avivi, Januario E Castro, Jason R Westin, Julio C Chavez, Armin Ghobadi, Krishna V Komanduri, Ronald Levy, Eric D Jacobsen, Thomas E Witzig, Patrick Reagan, Adrian Bot, John Rossi, Lynn Navale, Yizhou Jiang, Jeff Aycock, Meg Elias, David Chang, Jeff Wiezorek, William Y Go
Background In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. Methods In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine...
December 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29226764/chimeric-antigen-receptor-t-cells-in-refractory-b-cell-lymphomas
#6
Stephen J Schuster, Jakub Svoboda, Elise A Chong, Sunita D Nasta, Anthony R Mato, Özlem Anak, Jennifer L Brogdon, Iulian Pruteanu-Malinici, Vijay Bhoj, Daniel Landsburg, Mariusz Wasik, Bruce L Levine, Simon F Lacey, Jan J Melenhorst, David L Porter, Carl H June
Background Patients with diffuse large B-cell lymphoma or follicular lymphoma that is refractory to or that relapses after immunochemotherapy and transplantation have a poor prognosis. High response rates have been reported with the use of T cells modified by chimeric antigen receptor (CAR) that target CD19 in B-cell cancers, although data regarding B-cell lymphomas are limited. Methods We used autologous T cells that express a CD19-directed CAR (CTL019) to treat patients with diffuse large B-cell lymphoma or follicular lymphoma that had relapsed or was refractory to previous treatments...
December 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29226611/enhancing-the-stability-and-immunomodulatory-activity-of-liposomal-spherical-nucleic-acids-through-lipid-tail-dna-modifications
#7
Brian Meckes, Resham J Banga, SonBinh T Nguyen, Chad A Mirkin
Liposomal spherical nucleic acids (LSNAs) are an attractive therapeutic platform for gene regulation and immunomodulation due to their biocompatibility, chemically tunable structures, and ability to enter cells rapidly without the need for ancillary transfection agents. Such structures consist of small (<100 nm) liposomal cores functionalized with a dense, highly oriented nucleic acid shell, both of which are key components in facilitating their biological activity. Here, the properties of LSNAs synthesized using conventional methods, anchoring cholesterol terminated oligonucleotides into a liposomal core, are compared to LSNAs made by directly modifying the surface of a liposomal core containing azide-functionalized lipids with dibenzocyclooctyl-terminated oligonucleotides...
December 11, 2017: Small
https://www.readbyqxmd.com/read/29226489/inhibitory-effect-of-sulphated-polysaccharide-porphyran-isolated-from-porphyra-yezoensis-on-rankl-induced-differentiation-of-raw264-7-cells-into-osteoclasts
#8
Mikinori Ueno, Kichul Cho, Shogo Isaka, Tomoki Nishiguchi, Kenichi Yamaguchi, Daekyung Kim, Tatsuya Oda
Safe and efficient therapeutic agents for bone diseases are required in natural sources. We previously found that edible seaweed-derived polysaccharide porphyran exhibited anti-inflammatory effects through the down regulation of nuclear factor-κB. The aim of this study was to investigate the availability of porphyran as a therapeutic agent for bone diseases. The effects of porphyran on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells were examined. Porphyran suppressed RANKL-induced osteoclast formation in a concentration-dependent manner (6...
December 11, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29225604/transcriptional-regulation-of-t-cell-lipid-metabolism-implications-for-plasma-membrane-lipid-rafts-and-t-cell-function
#9
REVIEW
George A Robinson, Kirsty E Waddington, Ines Pineda-Torra, Elizabeth C Jury
It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM) and form signaling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β), and sterol regulatory element-binding proteins in T-cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29225603/regulatory-t-cells-suppress-inflammation-and-blistering-in-pemphigoid-diseases
#10
Katja Bieber, Shijie Sun, Mareike Witte, Anika Kasprick, Foteini Beltsiou, Martina Behnen, Tamás Laskay, Franziska S Schulze, Elena Pipi, Niklas Reichhelm, René Pagel, Detlef Zillikens, Enno Schmidt, Tim Sparwasser, Kathrin Kalies, Ralf J Ludwig
Regulatory T cells (Tregs) are well known for their modulatory functions in adaptive immunity. Through regulation of T cell functions, Tregs have also been demonstrated to indirectly curb myeloid cell-driven inflammation. However, direct effects of Tregs on myeloid cell functions are insufficiently characterized, especially in the context of myeloid cell-mediated diseases, such as pemphigoid diseases (PDs). PDs are caused by autoantibodies targeting structural proteins of the skin. Autoantibody binding triggers myeloid cell activation through specific activation of Fc gamma receptors, leading to skin inflammation and subepidermal blistering...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29225597/tregs-where-we-are-and-what-comes-next
#11
REVIEW
Hai Zhao, Xuelian Liao, Yan Kang
Regulatory T cells are usually recognized as a specialized subset of CD4+ T cells functioning in establishment and maintenance of immune tolerance. Meanwhile, there is emerging evidence that regulatory T cells (Tregs) are also present in various non-lymphoid tissues, and that they have unique phenotypes credited with activities distinct from regulatory function. Their development and function have been described in plenty of manuscripts in the past two decades. However, with the deepening of research in recent years, emerging evidence revealed some novel mechanisms about how Tregs exert their activities...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29225464/apolipoprotein-e3-mediated-cellular-uptake-of-reconstituted-high-density-lipoprotein-bearing-core-3-10-or-17-nm-hydrophobic-gold-nanoparticles
#12
Skylar T Chuang, Young-Seok Shon, Vasanthy Narayanaswami
We have developed a high-density lipoprotein (HDL)-based platform for transport and delivery of hydrophobic gold nanoparticles (AuNPs). The ability of apolipoprotein E3 (apoE3) to act as a high-affinity ligand for the low-density lipoprotein receptor (LDLr) was exploited to gain entry of HDL with AuNPs into glioblastoma cells. AuNPs of 3, 10, and 17 nm diameter, the latter two synthesized by phase transfer process, were solubilized by integration with phospholipids and apoE3, yielding reconstituted HDL (rHDL) bearing AuNPs...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29225340/genetic-and-experimental-evidence-for-the-involvement-of-the-cd6-lymphocyte-receptor-in-psoriasis
#13
Marta Consuegra-Fernández, Marc Julià, Mario Martínez-Florensa, Fernando Aranda, Cristina Català, Noelia Armiger-Borràs, María-Teresa Arias, Francisca Santiago, Antonio Guilabert, Anna Esteve, Carlos Muñoz, Carlos Ferrándiz, José-Manuel Carrascosa, Edurne Pedrosa, Jorge Romaní, Mercè Alsina, José-Manuel Mascaró-Galy, Francisco Lozano
Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors. Available evidence supports CD6, a lymphocyte surface receptor mostly expressed by T cells, as a putative target in autoimmunity. Accordingly, a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders, including psoriasis. Here, we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology. First, an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice, as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines, namely, interleukin-17A...
December 11, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29224741/identification-of-d-seco-modified-steroid-derivatives-with-affinity-for-estrogen-receptor-%C3%AE-and-%C3%AE-isoforms-using-a-non-transcriptional-fluorescent-cell-assay-in-yeast
#14
Sofija S Bekić, Maja A Marinović, Edward T Petri, Marija N Sakač, Andrea R Nikolić, Vesna V Kojić, Andjelka S Ćelić
Synthesis and biological evaluation of steroidal derivatives with anticancer properties is an active area of drug discovery. Here we measured the relative affinities of D-seco modified steroidal derivatives for estrogen receptor α, estrogen receptor β or androgen receptor ligand binding domains using an optimized non-transcriptional fluorescent cell assay in yeast. Ligand binding domains of steroid receptors were expressed in-frame with yellow fluorescent protein in the yeast Sacharomyces cerevisiae. Addition of known steroid ligands to yeast expressing the appropriate cognate receptor results in increased fluorescence intensity, enabling estimation of receptor binding affinities in a dose-response and time-dependent manner...
December 7, 2017: Steroids
https://www.readbyqxmd.com/read/29224077/gene-profiling-and-t-cell-receptor-sequencing-from-antigen-specific-cd4-t-cells
#15
Marie Holt, Anne Costanzo, Louis Gioia, Brian Abe, Andrew I Su, Luc Teyton
The paucity of pathogenic T cells in circulating blood limits the information delivered by bulk analysis. Toward diagnosis and monitoring of treatments of autoimmune diseases, we have devised single-cell analysis approaches capable of identifying and characterizing rare circulating CD4 T cells.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29223677/the-hypothalamus-pituitary-gonad-axis-tales-of-mice-and-men
#16
REVIEW
Athina Kaprara, Ilpo T Huhtaniemi
Reproduction is controlled by the hypothalamic - pituitary - gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons play a central role in this axis through production of GnRH, which binds to a membrane receptor on pituitary gonadotrophs and stimulates the biosynthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Multiple factors affect GnRH neuron migration, GnRH gene expression, GnRH pulse generator, GnRH secretion, GnRH receptor expression, and gonadotropin synthesis and release...
December 6, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29223395/a-novel-mouse-model-for-tracking-the-fate-of-cxcr5-expressing-t-cells
#17
Tomo Takebe, Kazuki Sakamoto, Yoshikazu Higami, Yohsuke Harada
The germinal center (GC) reaction, a critical process in the humoral immune response, requires follicular helper T (Tfh) cells. Tfh cells express the master transcription factor Bcl6 and chemokine receptor CXCR5, which enable them to migrate from the T cell zone to B cell follicles and interact with GC B cells. However, CXCR5 is downregulated when Tfh cells become memory cells. Therefore, it is difficult to track Tfh cells continuously in vivo. In this study, we generated a mouse strain, Cxcr5CreERT2R26Tomato, in which the fluorescent protein tdTomato is inducibly expressed in CXCR5+ cells by tamoxifen administration...
December 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29223294/glucocorticoid-hormone-treatment-enhances-the-cytokine-production-of-regulatory-t-cells-by-upregulation-of-foxp3-expression
#18
Emese Ugor, Lilla Prenek, Ramóna Pap, Gergely Berta, Dávid Ernszt, József Najbauer, Péter Németh, Ferenc Boldizsár, Tímea Berki
OBJECTIVE: Despite the fact that glucocorticoids (GC) are important therapeutic tools, their effects on regulatory T cells (Treg) are not well defined. The aim of our work was to investigate how GCs influence in vivo the thymic (tTreg) and peripheral Treg (pTreg) differentiation, survival and cytokine production. METHODS: Tregs were detected with flow cytometry in lymphatic organs of 4-6 weeks old BALB/c mice after repeated (2-4days), high-dose in vivo GC treatment using CD4/CD25 cell surface and Foxp3/IL-10/TGFβ/glucocorticoid receptor (GR) intracellular staining...
October 6, 2017: Immunobiology
https://www.readbyqxmd.com/read/29223138/plant-expressed-fc-fusion-protein-tetravalent-dengue-vaccine-with-inherent-adjuvant-properties
#19
Mi Young Kim, Alastair Copland, Kaustuv Nayak, Anmol Chandele, Muhammad Shamsher Ahmed, Qibo Zhang, Gil Reynolds Diogo, Matthew John Paul, Sven Hofmann, Moon-Sik Yang, Yong-Suk Jang, Julian K-C Ma, Rajko Reljic
Dengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi-Pasteur Denvaxia vaccine does not protect children under the age of nine and additional vaccine strategies are thus needed to halt this expanding global epidemic. Here, we employed a molecular engineering approach and plant-expression to produce a humanised and highly immunogenic Poly-Immunoglobulin G Scaffold (PIGS) fused to the consensus dengue envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor targeted vaccine candidate was demonstrated in transgenic mice expressing human FcγRI/CD64, by induction of neutralising antibodies and evidence of cell-mediated immunity...
December 9, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29222810/monocytes-enhance-neutrophil-induced-blister-formation-in-an-ex-vivo-model-of-bullous-pemphigoid
#20
E de Graauw, C Sitaru, M P Horn, L Borradori, S Yousefi, D Simon, H-U Simon
BACKGROUND: Lesions of bullous pemphigoid (BP), an autoimmune subepidermal blistering disease characterized by the presence of tissue-bound and circulating autoantibodies to hemidesmosomal antigens, harbour a mixed inflammatory cellular infiltrate. In various models, neutrophils, eosinophils, mast cells, monocytes as well as B and T cells have been shown to be involved in the pathogenesis of BP. However, their interactions with and effective role in blister formation remains uncertain...
December 8, 2017: Allergy
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