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https://www.readbyqxmd.com/read/28535666/ddx53-regulates-cancer-stem-cell-like-properties-by-binding-to-sox-2
#1
Youngmi Kim, Minjeong Yeon, Dooil Jeoung
This study investigated the role of cancer/testis antigen DDX53 in regulating cancer stem cell-like properties. DDX53 shows co-expression with CD133, a marker for cancer stem cells. DDX53 directly regulates the SOX-2 expression in anticancer drug-resistant Malme3MR cells. DDX53 and miR-200bwere found to be involved in the regulation of tumor spheroid forming potential of Malme3M and Malme3MR cells. Furthermore, the self-renewal activity and the tumorigenic potential of Malme3M(R)-CD133 (+) cells were also regulated by DDX53...
May 2, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28533414/manipulating-dna-damage-response-signaling-for-the-treatment-of-immune-mediated-diseases
#2
Jonathan P McNally, Scott H Millen, Vandana Chaturvedi, Nora Lakes, Catherine E Terrell, Eileen E Elfers, Kaitlin R Carroll, Simon P Hogan, Paul R Andreassen, Julie Kanter, Carl E Allen, Michael M Henry, Jay N Greenberg, Stephan Ladisch, Michelle L Hermiston, Michael Joyce, David A Hildeman, Jonathan D Katz, Michael B Jordan
Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28530714/cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes-arise-from-two-main-thymic-precursors
#3
Roland Ruscher, Rebecca L Kummer, You Jeong Lee, Stephen C Jameson, Kristin A Hogquist
TCRαβ(+)CD4(-)CD8α(+)CD8β(-) intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) through analysis of its maturation, localization and emigration. We defined two precursor populations among TCRβ(+)CD4(-)CD8(-) thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria. Those IELp populations included a nascent PD-1(+) population and a T-bet(+) population that accumulated with age...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28529699/evolution-immunity-and-the-emergence-of-brain-superautoantigens
#4
Serge Nataf
While some autoimmune disorders remain extremely rare, others largely predominate the epidemiology of human autoimmunity. Notably, these include psoriasis, diabetes, vitiligo, thyroiditis, rheumatoid arthritis and multiple sclerosis. Thus, despite the quasi-infinite number of "self" antigens that could theoretically trigger autoimmune responses, only a limited set of antigens, referred here as superautoantigens, induce pathogenic adaptive responses. Several lines of evidence reviewed in this paper indicate that, irrespective of the targeted organ (e...
2017: F1000Research
https://www.readbyqxmd.com/read/28526137/cellular-and-molecular-mechanisms-of-autoimmunity-and-lupus-nephritis
#5
S K Devarapu, G Lorenz, O P Kulkarni, H-J Anders, S R Mulay
Autoimmunity involves immune responses directed against self, which are a result of defective self/foreign distinction of the immune system, leading to proliferation of self-reactive lymphocytes, and is characterized by systemic, as well as tissue-specific, inflammation. Numerous mechanisms operate to ensure the immune tolerance to self-antigens. However, monogenetic defects or genetic variants that weaken immune tolerance render susceptibility to the loss of immune tolerance, which is further triggered by environmental factors...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28524357/double-caging-linker-for-and-type-fluorogenic-construction-of-protein-antibody-bioconjugates-and-in-situ-quantification
#6
Shiyong Liu, Guhuan Liu, Guohai Shi, Haoyue Sheng, Yanyan Jiang, Haojun Liang
We report on in situ fluorescent quantification of the conjugation efficiency between azide-terminated synthetic polymers/ imaging probes and thiol-functionalized antibodies/proteins/peptides, by utilizing a doubly caged profluorescent and heterodifunctional core molecule (C1) as the self-sorting bridging unit. Orthogonal dual 'click' coupling of C1 with azide- and thiol-functionalized precursors leads to highly fluorescent bioconjugates, whereas single click products of C1 remain essentially nonfluorescent...
May 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28522358/self-tolerance-and-autoimmunity-in-a-minimal-model-of-the-idiotypic-network
#7
Stefan Landmann, Nicolas Preuss, Ulrich Behn
We consider self-tolerance and its failure -autoimmunity- in a minimal mathematical model of the idiotypic network. A node in the network represents a clone of B-lymphocytes and its antibodies of the same idiotype which is encoded by a bitstring. The links between nodes represent possible interactions between clones of almost complementary idiotype. A clone survives only if the number of populated neighbored nodes is neither too small nor too large. The dynamics is driven by the influx of lymphocytes with randomly generated idiotype from the bone marrow...
May 15, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28522297/three-dimensional-spheroid-culture-promotes-the-stemness-maintenance-of-cranial-stem-cells-by-activating-pi3k-akt-and-suppressing-nf-%C3%AE%C2%BAb-pathways
#8
Da He, Ren-Xian Wang, Jian-Ping Mao, Bin Xiao, Da-Fu Chen, Wei Tian
Multipotent stem cells are one of the most powerful tools available for the bone regeneration. However, owing to various limitations, including a lack of tissue-specific stem cell identification, reconstruction of large cranial bone defects remains challenging. In the current study, we isolated a population of Sca-1(+)CD105(+)CD140a(+) stem cells from adult mouse calvarium and cultured them as three-dimensional spheroids. Although these cells shared similar surface antigens when grown in either monolayers or spheroids, the cranial stem cells grown in spheroids possessed enhanced multipotency and proliferation capacity...
May 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28522213/harnessing-self-assembled-peptide-nanoparticles-in-epitope-vaccine-design
#9
REVIEW
Manica Negahdaripour, Nasim Golkar, Nasim Hajighahramani, Sedigheh Kianpour, Navid Nezafat, Younes Ghasemi
Vaccination has been one of the most successful breakthroughs in medical history. In recent years, epitope-based subunit vaccines have been introduced as a safer alternative to traditional vaccines. However, they suffer from limited immunogenicity. Nanotechnology has shown value in solving this issue. Different kinds of nanovaccines have been employed, among which virus-like nanoparticles (VLPs) and self-assembled peptide nanoparticles (SAPNs) seem very promising. Recently, SAPNs have attracted special interest due to their unique properties, including molecular specificity, biodegradability, and biocompatibility...
May 15, 2017: Biotechnology Advances
https://www.readbyqxmd.com/read/28521905/harnessing-the-properties-of-dendritic-cells-in-the-pursuit-of-immunological-tolerance
#10
REVIEW
Christopher Horton, Kumaran Shanmugarajah, Paul J Fairchild
The acquisition of self-perpetuating, immunological tolerance specific for graft alloantigens has long been described as the "holy grail" of clinical transplantation. By removing the need for life-long immunosuppression following engraftment, the adverse consequences of immunosuppressive regimens, including chronic infections and malignancy, may be avoided. Furthermore, autoimmune diseases and allergy are, by definition, driven by aberrant immunological responses to ordinarily innocuous antigens. The re-establishment of permanent tolerance towards instigating antigens may, therefore, provide a cure to these common diseases...
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28516867/the-link-between-proteus-mirabilis-environmental-factors-and-autoantibodies-in-rheumatoid-arthritis
#11
REVIEW
Taha Rashid, Alan Ebringer, Clyde Wilson
Rheumatoid arthritis (RA) is a relatively common and potentially disabling immune-mediated inflammatory systemic disease, predominantly affecting women and characterised by multiple small joint arthritis. Extensive data supports the roles of genetic, environmental and microbial factors in the triggering and development of this disease. Proteus mirabilis is considered as the main microbial culprit in the causation of RA. The evidence for the role of these microbes in RA and their links with commonly associated autoantibodies such as rheumatoid factors and anti-citrullinated peptide antibodies have been elucidated together with their relations with some of the non-microbial environmental factors which have been implicated in the aetiopathogenesis of RA...
May 8, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28515356/licensing-delineates-helper-and-effector-nk-cell-subsets-during-viral-infection
#12
Anthony E Zamora, Ethan G Aguilar, Can M Sungur, Lam T Khuat, Cordelia Dunai, G Raymond Lochhead, Juan Du, Claire Pomeroy, Bruce R Blazar, Dan L Longo, Jeffrey M Venstrom, Nicole Baumgarth, William J Murphy
Natural killer (NK) cells can be divided into phenotypic subsets based on expression of receptors that bind self-MHC-I molecules, a concept termed licensing or education. Here we show NK cell subsets with different migratory, effector, and immunoregulatory functions in dendritic cell and antigen (ag)-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells localized in draining lymph nodes and produced GM-CSF, which correlated with the expansion and activation of dendritic cells, and resulted in greater and sustained ag-specific T cell responses...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28515133/development-of-a-novel-virus-like-particle-vaccine-platform-that-mimics-immature-form-of-alphavirus
#13
Akane Urakami, Atsuko Sakurai, Momoko Ishikawa, Moh Lan Yap, Yevel Flores-Garcia, Yasunari Haseda, Taiki Aoshi, Fidel P Zavala, Michael G Rossmann, Sachiko Kuno, Ryuji Ueno, Wataru Akahata
Virus-like particles (VLPs) are non-infectious multiprotein structures that are engineered to self-assemble from viral structural proteins. Here, we developed a novel VLP-based vaccine platform utilizing VLPs from the Chikungunya virus. We identified two regions within the envelope protein, a structural component of Chikungunya, where foreign antigens can be inserted without compromising VLP structure. Our VLP displays 480 copious copies of an inserted antigen on the VLP surface in a highly symmetric manner, thus capable of inducing strong immune responses against any inserted antigen...
May 17, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28514438/conversion-of-adult-endothelium-to-immunocompetent-haematopoietic-stem-cells
#14
Raphael Lis, Charles C Karrasch, Michael G Poulos, Balvir Kunar, David Redmond, Jose G Barcia Duran, Chaitanya R Badwe, William Schachterle, Michael Ginsberg, Jenny Xiang, Arash Rafii Tabrizi, Koji Shido, Zev Rosenwaks, Olivier Elemento, Nancy A Speck, Jason M Butler, Joseph M Scandura, Shahin Rafii
Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28513983/book-review-the-foundations-of-immunology-and-their-pertinence-to-medicine
#15
REVIEW
A Corthay
We are in the era cursed with overspecialization. Charles Darwin's foundational Origin of Species, published in 1859 was accessible to the broadly educated individual. Starting with this statement, Peter Bretscher in his new book aims at explaining foundational concepts of immunology to a broad public. His standpoint is that foundational ideas usually can be simply expressed. This book describes first how foundational concepts of immunology have evolved over the last two and a half centuries. The importance of self-nonself discrimination by the immune system is acknowledged and models for immunological tolerance are compared...
May 17, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28512459/in-vivo-chronic-stimulation-unveils-autoreactive-potential-of-wiskott-aldrich-syndrome-protein-deficient-b-cells
#16
Maria Carmina Castiello, Francesca Pala, Lucia Sereni, Elena Draghici, Donato Inverso, Aisha V Sauer, Francesca Schena, Elena Fontana, Enrico Radaelli, Paolo Uva, Karla E Cervantes-Luevano, Federica Benvenuti, Pietro L Poliani, Matteo Iannacone, Elisabetta Traggiai, Anna Villa, Marita Bosticardo
Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency caused by mutations in the gene encoding the hematopoietic-specific WAS protein (WASp). WAS is frequently associated with autoimmunity, indicating a critical role of WASp in maintenance of tolerance. The role of B cells in the induction of autoreactive immune responses in WAS has been investigated in several settings, but the mechanisms leading to the development of autoimmune manifestations have been difficult to evaluate in the mouse models of the disease that do not spontaneously develop autoimmunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#17
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506535/sca-1-expression-level-identifies-quiescent-hematopoietic-stem-and-progenitor-cells
#18
Mina N F Morcos, Kristina B Schoedel, Anja Hoppe, Rayk Behrendt, Onur Basak, Hans C Clevers, Axel Roers, Alexander Gerbaulet
Blood cell generation depends on continuous cellular output by the sequential hierarchy of hematopoietic stem cell (HSC) and progenitor populations that all contain quiescent and actively cycling cells. Hematopoietic stem and progenitor cells (HSPCs) express the surface molecule Stem cell antigen 1 (SCA-1/LY6A). Using histone 2B-red fluorescent fusion protein label retention and cell-cycle reporter mice, we demonstrate that high SCA-1 expression (SCA-1(hi)) identifies not only quiescent HSCs but quiescent cells on all hierarchical levels within the lineage(-)SCA-1(+)KIT(+) (LSK) population...
May 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28505198/strongyloides-seroprevalence-before-and-after-an-ivermectin-mass-drug-administration-in-a-remote-australian-aboriginal-community
#19
Therese M Kearns, Bart J Currie, Allen C Cheng, James McCarthy, Jonathan R Carapetis, Deborah C Holt, Wendy Page, Jennifer Shield, Roslyn Gundjirryirr, Eddie Mulholland, Linda Ward, Ross M Andrews
BACKGROUND: Strongyloides seroprevalence is hyper-endemic in many Australian Aboriginal and Torres Strait Islander communities, ranging from 35-60%. We report the impact on Strongyloides seroprevalence after two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. METHODS: Utilizing a before and after study design, we measured Strongyloides seroprevalence through population census with sequential MDAs at baseline and month 12...
May 15, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28505143/the-transcriptome-of-type-i-murine-astrocytes-under-interferon-gamma-exposure-and-remyelination-stimulus
#20
Anna Kudriaeva, Vladimir V Galatenko, Diana V Maltseva, Nadezhda A Khaustova, Ekaterina Kuzina, Alexander G Tonevitsky, Alexander Gabibov, Alexey Belogurov
Astrocytes are considered to be an important contributor to central nervous system (CNS) disorders, particularly multiple sclerosis. The transcriptome of these cells is greatly affected by cytokines released by lymphocytes, penetrating the blood-brain barrier-in particular, the classical pro-inflammatory cytokine interferon-gamma (IFNγ). We report here the transcriptomal profiling of astrocytes treated using IFNγ and benztropine, a putative remyelinization agent. Our findings indicate that the expression of genes involved in antigen processing and presentation in astrocytes are significantly upregulated upon IFNγ exposure, emphasizing the critical role of this cytokine in the redirection of immune response towards self-antigens...
May 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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