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Immune deficiency

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https://www.readbyqxmd.com/read/28651122/activation-of-irf3-contributes-to-ifn-%C3%AE-and-isg54-expression-during-the-immune-responses-to-b16f10-tumor-growth
#1
Zachary Guinn, Deborah M Brown, Thomas M Petro
Interferon Regulatory Factor (IRF-3) has been shown to contribute to immune control of B16 melanoma tumor growth. We have shown previously that IRF-3 has a role in IFN-γ-induced expression of pro-apoptotic interferon stimulated gene 54 (ISG54) in macrophages and IFN-γ in T cells. To investigate the IRF3-IFN-γ-ISG54 nexus, we injected C57Bl/6 (B6) and IRF3KO mice s.c. with luciferase-producing B16-F10 tumor cells. Tumor growth as measured by luciferase levels was similar between B6 and IRF3KO mice at days 2 and 6, but was significantly greater at day 9 in IRF3KO mice compared with B6 mice...
June 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28650995/septins-restrict-inflammation-and-protect-zebrafish-larvae-from-shigella-infection
#2
Maria J Mazon-Moya, Alexandra R Willis, Vincenzo Torraca, Laurent Boucontet, Avinash R Shenoy, Emma Colucci-Guyon, Serge Mostowy
Shigella flexneri, a Gram-negative enteroinvasive pathogen, causes inflammatory destruction of the human colonic epithelium. Infection by S. flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system. Recent work has revealed that components of the cytoskeleton have important functions in innate immunity and inflammation control. Septins, highly conserved cytoskeletal proteins, have emerged as key players in innate immunity to bacterial infection, yet septin function in vivo is poorly understood...
June 26, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28648928/pg2-a-botanically-derived-drug-extracted-from-astragalus-membranaceus-promotes-proliferation-and-immunosuppression-of-umbilical-cord-derived-mesenchymal-stem-cells
#3
Yu-Hua Chao, Kang-Hsi Wu, Chiao-Wen Lin, Shun-Fa Yang, Wan-Ru Chao, Ching-Tien Peng, Han-Ping Wu
ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus membranaceus is used to manage the deficiency of vital energy in traditional Chinese medicine and confirmed to have many biological functions. Mesenchymal stem cells (MSCs) possess immunosuppressive effects, and are widely used for regenerative medicine and immune disorders. AIMS OF STUDY: This study investigated the effects of Astragalus polysaccharides (APS) on umbilical cord-derived MSCs (UCMSCs), including morphology, surface marker expression, proliferation, differentiation, and in-vitro and in-vivo immunosuppressive capacities...
June 22, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28648734/drug-induced-hemolytic-anemia-pharmacological-aspects
#4
D Renard, A Rosselet
Drug-induced hemolytic anemia is a very rare but potentially lethal adverse drug reaction, which can take the form of oxidative damage to vulnerable erythrocytes (as in glucose-6-phosphate dehydrogenase deficiency), drug-induced thrombotic microangiopathy, or immune-mediated hemolytic anemia. For each form, distinctive drugs are documented as potential triggers. When a formal diagnosis of hemolytic anemia is made following drug administration, a structured approach is recommended to assess the plausibility of an adverse drug reaction based on chronological sequence, epidemiological data, objective evidence (when available), and ruling out of non-drug causes...
June 22, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28647590/differences-in-the-coronal-proteome-acquired-by-particles-depositing-in-the-lungs-of-asthmatic-versus-healthy-humans
#5
Abhinav Kumar, Elif Melis Bicer, Paul Pfeffer, Marco P Monopoli, Kenneth A Dawson, Jonny Eriksson, Katarina Edwards, Steven Lynham, Matthew Arno, Annelie F Behndig, Anders Blomberg, Graham Somers, Dave Hassall, Lea Ann Dailey, Ben Forbes, Ian Mudway
Most inhaled nanomedicines in development are for the treatment of lung disease, yet little is known about their interaction with the respiratory tract lining fluids (RTLF). Here we combined the use of nano-silica, as a protein concentrator, with label-free snapshot proteomics (LC-MS/MS; key findings confirmed by ELISA) to generate a quantitative profile of the RTLF proteome and provided insight into the evolved corona; information that may be used in future to improve drug targeting to the lungs by inhaled medicines...
June 21, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28646899/immunoproteasome-deficiency-alters-microglial-cytokine-response-and-improves-cognitive-deficits-in-alzheimer-s-disease-like-appps1-mice
#6
Lisa K Wagner, Kate E Gilling, Eileen Schormann, Peter M Kloetzel, Frank L Heppner, Elke Krüger, Stefan Prokop
The immunoproteasome (iP) represents a specialized type of proteasomes, which plays an important role in the clearance of oxidant-damaged proteins under inflammatory and pathological conditions determining the outcome of various diseases. In Alzheimer's disease (AD)-like APPPS1 mice Aβ-deposition is paralleled by iP upregulation, most likely mediated through type I interferon induction. To define the impact of increased iP expression we crossed APPPS1 mice with mice deficient in the iP subunit LMP7 resulting in impaired iP function...
June 24, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28646085/generation-of-a-collection-of-mutant-tomato-lines-using-pooled-crispr-libraries
#7
Thomas B Jacobs, Ning Zhang, Dhruv Patel, Gregory B Martin
The high efficiency of CRIPSR-mediated mutagenesis in plants enables the development of high-throughput mutagenesis strategies. By transforming pooled CRISPR libraries into tomato, collections of mutant lines were generated with minimal transformation attempts and in a relatively short period of time. Identification of the targeted gene(s) was easily determined by sequencing the incorporated gRNA(s) in the primary transgenic events. From a single transformation with a CRISPR library targeting the immunity-associated leucine-rich repeat subfamily XII genes, heritable mutations were recovered in 15 of the 54 genes targeted...
June 23, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28646076/transcriptomic-and-proteomic-profiling-provides-insight-into-mesangial-cell-function-in-iga-nephropathy
#8
Peidi Liu, Emelie Lassén, Viji Nair, Celine C Berthier, Miyuki Suguro, Carina Sihlbom, Matthias Kretzler, Christer Betsholtz, Börje Haraldsson, Wenjun Ju, Kerstin Ebefors, Jenny Nyström
IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22)...
June 23, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28646042/on-the-role-il-4-il-13-heteroreceptor-plays-in-regulation-of-type-1-diabetes
#9
Tobechukwu K Ukah, Alexis N Cattin-Roy, Weirong Chen, Mindy M Miller, Subhasis Barik, Habib Zaghouani
Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#10
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645775/altered-populations-of-natural-killer-cells-cytotoxic-t-lymphocytes-and-regulatory-t-cells-in-major-depressive-disorder-association-with-sleep-disturbance
#11
Hideo Suzuki, Jonathan Savitz, T Kent Teague, Siva K Gandhapudi, Chibing Tan, Masaya Misaki, Brett A McKinney, Michael R Irwin, Wayne C Drevets, Jerzy Bodurka
A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations...
June 20, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28645564/immunotherapy-holds-the-key-to-cancer-treatment-and-prevention-in-constitutional-mismatch-repair-deficiency-cmmrd-syndrome
#12
Harm Westdorp, Sigrid Kolders, Nicoline Hoogerbrugge, I Jolanda M de Vries, Marjolijn C J Jongmans, Gerty Schreibelt
Monoallelic germline mutations in one of the DNA mismatch repair (MMR) genes cause Lynch syndrome, with a high lifetime risks of colorectal and endometrial cancer at adult age. Less well known, is the constitutional mismatch repair deficiency (CMMRD) syndrome caused by biallelic germline mutations in MMR genes. This syndrome is characterized by the development of childhood cancer. Patients with CMMRD are at extremely high risk of developing multiple cancers including hematological, brain and intestinal tumors...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28645311/zika-virus-tropism-and-interactions-in-myelinating-neural-cell-cultures-cns-cells-and-myelin-are-preferentially-affected
#13
Stephanie L Cumberworth, Jennifer A Barrie, Madeleine E Cunningham, Daniely Paulino Gomes de Figueiredo, Verena Schultz, Adrian J Wilder-Smith, Benjamin Brennan, Lindomar J Pena, Rafael Freitas de Oliveira França, Christopher Linington, Susan C Barnett, Hugh J Willison, Alain Kohl, Julia M Edgar
The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV...
June 23, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28645307/aberrant-intestinal-microbiota-due-to-il-1-receptor-antagonist-deficiency-promotes-il-17-and-tlr4-dependent-arthritis
#14
Rebecca Rogier, Thomas H A Ederveen, Jos Boekhorst, Harm Wopereis, Jose U Scher, Julia Manasson, Sanne J C M Frambach, Jan Knol, Johan Garssen, Peter M van der Kraan, Marije I Koenders, Wim B van den Berg, Sacha A F T van Hijum, Shahla Abdollahi-Roodsaz
BACKGROUND: Perturbation of commensal intestinal microbiota has been associated with several autoimmune diseases. Mice deficient in interleukin-1 receptor antagonist (Il1rn (-/-) mice) spontaneously develop autoimmune arthritis and are susceptible to other autoimmune diseases such as psoriasis, diabetes, and encephalomyelitis; however, the mechanisms of increased susceptibility to these autoimmune phenotypes are poorly understood. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) in regulation of commensal intestinal microbiota, and assessed the involvement of microbiota subsets and innate and adaptive mucosal immune responses that underlie the development of spontaneous arthritis in Il1rn (-/-) mice...
June 23, 2017: Microbiome
https://www.readbyqxmd.com/read/28644433/ctla-4-mediated-posttranslational-modifications-direct-cytotoxic-t-lymphocyte-differentiation
#15
Holger Lingel, Josef Wissing, Aditya Arra, Denny Schanze, Stefan Lienenklaus, Frank Klawonn, Mandy Pierau, Martin Zenker, Lothar Jänsch, Monika C Brunner-Weinzierl
The blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8(+) T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644354/development-and-function-of-immune-cells-in-an-adolescent-patient-with-a-deficiency-in-the-interleukin-10-receptor
#16
Sharon Veenbergen, Marieke A van Leeuwen, Gertjan J Driessen, Rogier Kersseboom, Lilian F de Ruiter, Rolien H C Raatgeep, Dicky J Lindenbergh-Kortleve, Ytje Simons-Oosterhuis, Katharina Biermann, Dicky J J Halley, Lissy de Ridder, Johanna C Escher, Janneke N Samsom
OBJECTIVE: Monogenic defects in the interleukin-10 (IL-10) pathway are extremely rare and cause infantile-onset inflammatory bowel disease (IBD)-like pathology. Understanding how immune responses are dysregulated in monogenic IBD-like diseases can provide valuable insight in "classical" IBD pathogenesis. Here, we studied long-term immune cell development and function in an adolescent IL-10 receptor (IL10RA)-deficient patient who presented in infancy with severe colitis and fistulizing perianal disease and is currently treated with immune suppressants...
July 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28643847/ncr1-deficiency-diminishes-the-generation-of-protective-murine-cytomegalovirus-antibodies-by-limiting-follicular-helper-t-cell-maturation
#17
Antonija Miletic, Maja Lenartic, Branka Popovic, Ilija Brizic, Tihana Trsan, Karmela Miklic, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
NKp46/NCR1 is an activating NK-cell receptor implicated in the control of various viral and bacterial infections. Recent findings also suggest that it plays a role in shaping the adaptive immune response to pathogens. Using NCR1-deficient (NCR1(gfp/gfp) ) mice we provide evidence for the role of NCR1 in antibody response to mouse cytomegalovirus infection (MCMV). The absence of NCR1 resulted in impaired maturation, function and NK-cell migration to regional lymph nodes. In addition, CD4(+) T-cell activation and follicular helper T-cell (Tfh) generation were reduced, leading to inferior germinal center (GC) B-cell maturation...
June 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28642819/adoptive-cell-therapy-using-pd-1-myeloma-reactive-t-cells-eliminates-established-myeloma-in-mice
#18
Weiqing Jing, Jill A Gershan, Grace C Blitzer, Katie Palen, James Weber, Laura McOlash, Matthew Riese, Bryon D Johnson
BACKGROUND: Adoptive cellular therapy (ACT) with cancer antigen-reactive T cells following lymphodepletive pre-conditioning has emerged as a potentially curative therapy for patients with advanced cancers. However, identification and enrichment of appropriate T cell subsets for cancer eradication remains a major challenge for hematologic cancers. METHODS: PD-1(+) and PD-1(-) T cell subsets from myeloma-bearing mice were sorted and analyzed for myeloma reactivity in vitro...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28642294/mhc-class-ii-invariant-chain-peptide-or-gamma-delta-t-cell-depletion-ameliorates-experimental-preeclampsia
#19
Piyali Chatterjee, Valorie L Chiasson, Geetha Seerangan, Eugene De Guzman, Moheb Milad, Kelsey R Bounds, Olga Gasheva, Richard P Tobin, Mohamad Hatahet, Shelley Kopriva, Kathleen A Jones, M Karen Newell-Rogers, Brett Mitchell
Excessive innate immune system activation and inflammation during pregnancy can lead to organ injury and dysfunction and preeclampsia; however, the molecular mechanisms involved are unknown.  We tested the hypothesis that Toll-like receptor activation induces MHC class II invariant chain peptide (CLIP) expression on immune cells, makes them pro-inflammatory, and are necessary to cause preeclampsia-like features in mice.  Treatment with VG1177, a competitive antagonist peptide for CLIP in the groove of MHC class II, was able to both prevent and treat preeclampsia-like features in mice...
June 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28642279/role-of-myd88-signaling-in-the-imiquimod-induced-mouse-model-of-psoriasis-focus-on-innate-myeloid-cells
#20
Sara Costa, Olivia Marini, Dalila Bevilacqua, Anthony L DeFranco, Baidong Hou, Silvia Lonardi, William Vermi, Pamela Rodegher, Anna Panato, Franco Tagliaro, Clifford A Lowell, Marco A Cassatella, Giampiero Girolomoni, Patrizia Scapini
Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88(fl/fl)Vav-cre(+) mice) with mice carrying the total MyD88 deficiency (Myd88(-/-) mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells...
June 22, 2017: Journal of Leukocyte Biology
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