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https://www.readbyqxmd.com/read/29328910/modulation-of-myelopoiesis-progenitors-is-an-integral-component-of-trained-immunity
#1
Ioannis Mitroulis, Klara Ruppova, Baomei Wang, Lan-Sun Chen, Michal Grzybek, Tatyana Grinenko, Anne Eugster, Maria Troullinaki, Alessandra Palladini, Ioannis Kourtzelis, Antonios Chatzigeorgiou, Andreas Schlitzer, Marc Beyer, Leo A B Joosten, Berend Isermann, Mathias Lesche, Andreas Petzold, Kai Simons, Ian Henry, Andreas Dahl, Joachim L Schultze, Ben Wielockx, Nicola Zamboni, Peter Mirtschink, Ünal Coskun, George Hajishengallis, Mihai G Netea, Triantafyllos Chavakis
Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation. We thus hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells (HSPCs). Administration of β-glucan (prototypical trained-immunity-inducing agonist) to mice induced expansion of progenitors of the myeloid lineage, which was associated with elevated signaling by innate immune mediators, such as IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF), and with adaptations in glucose metabolism and cholesterol biosynthesis...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328541/gm-csf-ameliorates-micro-vascular-barrier-integrity-via-pericytes-derived-ang-1-in-wound-healing
#2
Min Yan, Yange Hu, Min Yao, Shisan Bao, Yong Fang
BACKGROUND: Skin wound healing involves complex coordinated interactions of cells, tissues and mediators. Maintaining microvascular barrier integrity is one of the key events for endothelial homeostasis during wound healing. Vasodilation is observed after vasoconstriction, which causes blood vessels to become porous, facilitates leukocyte infiltration and aids angiogenesis at the wound-area, post-injury. Eventually, vessel integrity has to be re-established for vascular maturation. Numerous studies have found that granulocyte macrophage colony-stimulating factor (GM-CSF) accelerates wound healing by inducing recruitment of repair cells into the injury area and releases of cytokines...
January 12, 2018: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/29319160/macrophage-plasticity-polarization-and-function-in-health-and-disease
#3
REVIEW
Abbas Shapouri Moghaddam, Saeed Mohammadian, Hossein Vazini, Mahdi Taghadosi, Seyed-Alireza Esmaeili, Fatemeh Mardani, Bita Seifi, Asadollah Mohammadi, Jalil Tavakol Afshari, Amirhossein Sahebkar
Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro-inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN-γ, GM-CSF and produce pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-12, IL-23 and TNF-α, and 2) Alternatively activated or M2 macrophages, which are anti-inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL-4 and IL-13 and produce anti-inflammatory cytokines such as IL-10 and TGF-β...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29318872/covalent-conjugation-of-peptide-antigen-to-mesoporous-silica-rods-to-enhance-cellular-responses
#4
Maxence O Dellacherie, Aileen W Li, Beverly Y Lu, David J Mooney
Short peptides are the minimal modality of antigen recognized by cellular immunity and are therefore considered a safe and highly specific source of antigen for vaccination. Nevertheless, successful peptide immunotherapy is limited by the short half-life of peptide antigens in vivo as well as their weak immunogenicity. We recently reported a vaccine strategy based on dendritic cell-recruiting Mesoporous Silica Rod (MSR) scaffolds to enhance T-cell responses against subunit antigen. In this study, we investigated the effect of covalently conjugating peptide antigens to MSRs to increase their retention in the scaffolds...
January 10, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29317300/mesenchymal-stem-cells-therapy-protects-fetuses-from-resorption-and-induces-th2-type-cytokines-profile-in-abortion-prone-mouse-model
#5
Amir Salek Farrokhi, Amir-Hassan Zarnani, Seyed Mohammad Moazzeni
The imbalance of Th1/Th2 cytokines is well known in recurrent spontaneous abortion (RSA) mouse model. Mesenchymal stem cells (MSCs) possess potent immunoregulatory properties that could modulate the Th1 cytokine responses in benefit of Th2 types. In this study, we aimed to analyze the local and systemic balance of Th1/Th2 cytokines following MSCs therapy. Syngeneic adipose derived MSCs were administered to abortion prone mice during the implantation window. The abortion rate was determined and IL-4, IL-6, IL-12, IL-2, IFN-γ and GM-CSF gene expression was evaluated by Real-Time-PCR in decidual and placental tissues of pregnant mice at day 13...
January 6, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29316343/circulating-monocyte-chemoattractant-protein-1-mcp-1-is-associated-with-cachexia-in-treatment-na%C3%A3-ve-pancreatic-cancer-patients
#6
Erin E Talbert, Heather L Lewis, Matthew R Farren, Mitchell L Ramsey, Jeffery M Chakedis, Priyani Rajasekera, Ericka Haverick, Angela Sarna, Mark Bloomston, Timothy M Pawlik, Teresa A Zimmers, Gregory B Lesinski, Phil A Hart, Mary E Dillhoff, Carl R Schmidt, Denis C Guttridge
BACKGROUND: Cancer-associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer-induced cachexia in patients with earlier stages of disease...
January 7, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29315951/four-way-multimodal-fusion-of-7%C3%A2-t-imaging-data-using-an-mcca-jica-model-in-first-episode-schizophrenia
#7
Kristin K Lottman, David M White, Nina V Kraguljac, Meredith A Reid, Vince D Calhoun, Fabio Catao, Adrienne C Lahti
Acquisition of multimodal brain imaging data for the same subject has become more common leading to a growing interest in determining the intermodal relationships between imaging modalities to further elucidate the pathophysiology of schizophrenia. Multimodal data have previously been individually analyzed and subsequently integrated; however, these analysis techniques lack the ability to examine true modality inter-relationships. The utilization of a multiset canonical correlation and joint independent component analysis (mCCA + jICA) model for data fusion allows shared or distinct abnormalities between modalities to be examined...
January 9, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29306096/embryotoxic-cytokines-potential-roles-in-embryo-loss-and-fetal-programming
#8
REVIEW
Sarah A Robertson, Peck-Yin Chin, Joseph G Femia, Hannah M Brown
Cytokines in the reproductive tract environment at conception mediate a dialogue between the embryo and maternal tissues to profoundly influence embryo development and implantation success. Through effects on gene expression and the cell stress response, cytokines elicit an epigenetic impact with consequences for placental development and fetal growth, which in turn affect metabolic phenotype and long-term health of offspring. There is substantial evidence demonstrating that pro-survival cytokines, such as GM-CSF, CSF1, LIF, HB-EGF and IGFII, support embryos to develop optimally...
December 27, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29304863/gm-csf-overexpression-after-influenza-a-virus-infection-prevents-mortality-and-moderates-m1-like-airway-monocyte-macrophage-polarization
#9
E Scott Halstead, Todd M Umstead, Michael L Davies, Yuka Imamura Kawasawa, Patricia Silveyra, Judie Howyrlak, Linlin Yang, Weichao Guo, Sanmei Hu, Eranda Kurundu Hewage, Zissis C Chroneos
BACKGROUND: Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established. METHODS: Mice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi)...
January 5, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29304171/mcp-1-kc-like-and-il-8-as-critical-mediators-of-pathogenesis-caused-by-babesia-canis
#10
Asier Galán, Iva Mayer, Renata Barić Rafaj, Krešo Bendelja, Velimir Sušić, José Joaquín Cerón, Vladimir Mrljak
Canine babesiosis caused by the intraerythrocytic protozoan parasite Babesia canis is a tick-borne disease characterized by a host response that involves both cellular and humoral immunity. This study focuses on the secretion of cytokines Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Keratinocyte Chemotactic-like (KC-like), Interleukins (IL)-2, IL-7, IL-8, IL-10, IL-15, IL-18 and Monocyte Chemotactic Protein-1 (MCP-1) in babesiosis caused by Babesia canis upon treatment with Imizol®. We assessed time dependent changes in cytokine levels and tested whether these changes correlate with pathogenesis of the disease...
2018: PloS One
https://www.readbyqxmd.com/read/29301935/-inhibition-of-histone-h3k27-demethylase-selectively-modulates-inflammatory-phenotypes-of-natural-killer-cells
#11
Adam Cribbs, Edward S Hookway, Graham Wells, Morten Lindow, Susanna Obad, Henrik Oerum, Rab K Prinjha, Nick Athanasou, Aneka Sowman, Martin Philpott, Henry Penn, Kalle Soderstrom, Marc Feldmann, Udo Oppermann
Natural killer (NK) cells are innate lymphocytes, important in immune surveillance and elimination of stressed, transformed, or virus-infected cells. They critically shape the inflammatory cytokine environment to orchestrate interactions of cells of the innate and adaptive immune systems. Some studies have reported that NK cell activation and cytokine secretion are controlled epigenetically, but have yielded only limited insight into the mechanisms. Using chemical screening with small-molecule inhibitors of chromatin methylation and acetylation, further validated by knockdown approaches, we here identified Jumonji-type histone H3K27 demethylases as key regulators of cytokine production in human NK cell subsets...
January 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29301342/small-myristoylated-protein-3-identified-as-a-potential-virulence-factor-in-leishmania-amazonensis-proves-to-be-a-protective-antigen-against-visceral-leishmaniasis
#12
Marcelo P Oliveira, Vívian T Martins, Thaís T O Santos, Daniela P Lage, Fernanda F Ramos, Beatriz C S Salles, Lourena E Costa, Daniel S Dias, Patrícia A F Ribeiro, Mônica S Schneider, Ricardo A Machado-de-Ávila, Antônio L Teixeira, Eduardo A F Coelho, Miguel A Chávez-Fumagalli
In a proteomics approach conducted with Leishmania amazonensis, parasite proteins showed either an increase or a decrease in their expression content during extensive in vitro cultivation, and were related to the survival and the infectivity of the parasites, respectively. In the current study, a computational screening was performed to predict virulence factors among these molecules. Three proteins were selected, one of which presented no homology to human proteins. This candidate, namely small myristoylated protein-3 (SMP-3), was cloned, and its recombinant version (rSMP-3) was used to stimulate peripheral blood mononuclear cells (PBMCs) from healthy subjects living in an endemic area of leishmaniasis and from visceral leishmaniasis patients...
January 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29296839/pak2-regulates-myeloid-derived-suppressor-cell-development-in-mice
#13
Yi Zeng, Seongmin Hahn, Jessica Stokes, Emely A Hoffman, Monika Schmelz, Maria Proytcheva, Jonathan Chernoff, Emmanuel Katsanis
Myeloid-derived suppressor cells (MDSCs) are CD11b+Gr1+ cells that induce T-cell hyporesponsiveness, thus impairing antitumor immunity. We have previously reported that disruption of Pak2, a member of the p21-activated kinases (Paks), in hematopoietic stem/progenitor cells (HSPCs) induces myeloid lineage skewing and expansion of CD11bhighGr1high cells in mice. In this study, we confirmed that Pak2-KO CD11bhighGr1high cells suppressed T-cell proliferation, consistent with an MDSC phenotype. Loss of Pak2 function in HSPCs led to (1) increased hematopoietic progenitor cell sensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, (2) increased MDSC proliferation, (3) decreased MDSC sensitivity to both intrinsic and Fas-Fas ligand-mediated apoptosis, and (4) promotion of MDSCs by Pak2-deficient CD4+ T cells that produced more interferon γ, tumor necrosis factor α, and GM-CSF...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296736/novel-gm-csf-signals-via-ifn-%C3%AE-r-irf-1-and-akt-mtor-license-monocytes-for-suppressor-function
#14
Eliana Ribechini, James A Hutchinson, Sabine Hergovits, Marion Heuer, Jörg Lucas, Ulrike Schleicher, Ana-Laura Jordán Garrote, Sarah J Potter, Paloma Riquelme, Heike Brackmann, Nora Müller, Hartmann Raifer, Ingolf Berberich, Magdalena Huber, Andreas Beilhack, Michael Lohoff, Christian Bogdan, Matthias Eyrich, Heike M Hermanns, Edward K Geissler, Manfred B Lutz
Granulocyte-macrophage colony-stimulating factor (GM-CSF) controls proliferation and survival of myeloid cells including monocytes. Here, we describe a time-dependent licensing process driven by GM-CSF in murine Ly6Chigh and human CD14+ monocytes that disables their inflammatory functions and promotes their conversion into suppressor cells. This 2-step licensing of monocytes requires activation of the AKT/mTOR/mTORC1 signaling cascade by GM-CSF followed by signaling through the interferon-γ receptor (IFN-γR)/interferon regulatory factor-1 (IRF-1) pathway...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29291452/ifn-%C3%AE-decreased-the-suppressive-function-of-cd33-hla-drlow-myeloid-cells-through-down-regulation-of-pd-1-pd-l2-signaling-pathway
#15
Xiaoxia Zhan, Shengfeng Hu, Yongjian Wu, Miao Li, Ting Liu, Siqi Ming, Minhao Wu, Min Liu, Xi Huang
Myeloid-derived suppressor cells (MDSCs) have recently been described to inhibit protective T-cell responses in tuberculosis (TB). T cells play an important role in the immunity to Mycobacterium tuberculosis, and are the major producers of IFN-γ. However, the impact of IFN-γ on MDSCs during TB is still not completely understood. Our study demonstrated a significant correlation between MDSC levels and TB progression, suggesting that MDSCs may serve as a potential marker in diagnosis or treatment of TB. Culture with GM-csf and IL-6 promoted peripheral blood mononuclear cells (PBMCs) to differentiate into functional CD33+HLA-DRlow MDSC-like cells...
December 29, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29290406/elevated-expression-of-granulocyte-macrophage-colony-stimulating-factor-receptor-in-multiple-sclerosis-lesions
#16
Jaime Imitola, Javad Rasouli, Fumihiro Watanabe, Kader Mahajan, Aswhini D Sharan, Bogoljub Ciric, Guang-Xian Zhang, Abdolmohamad Rostami
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease that disproportionately affects young adults, leading to disability and high costs to society. Infiltration of T cells and monocytes into the central nervous system (CNS) is critical for disease initiation and progression. However, despite a great deal of effort the molecular mechanisms by which immune cells initiate and perpetuate CNS damage in MS have not yet been elucidated. In experimental autoimmune encephalomyelitis (EAE), an animal model of MS, granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by pathogenic Th1 and Th17 cells is critical for the recruitment of monocytes into the CNS during the initial stage of disease...
December 22, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29288203/the-p38-mk2-3-module-is-critical-for-il-33-induced-signaling-and-cytokine-production-in-dendritic-cells
#17
Christiane Göpfert, Nico Andreas, Franziska Weber, Norman Häfner, Tatiana Yakovleva, Matthias Gaestel, Thomas Kamradt, Sebastian Drube
IL-33 is an IL-1 cytokine superfamily member. Binding of IL-33 to the IL-33R induces activation of the canonical NF-κB signaling and activation of MAPKs. In bone marrow-derived dendritic cells, IL-33 induces the production of IL-6, IL-13, and TNF-α. However, the signaling pathways resulting in IL-33-induced effector functions of dendritic cells are unknown. In this article, we show that the IL-33-induced cytokine production is only partly dependent on p65. Thereby, p65 mediates the production of IL-6, but not of IL-13, whereas the p38-Mapk-activated protein kinases 2/3 (MK2/3) signaling module mediates the IL-13, but not the IL-6, production...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29288202/gm-csf-promotes-chronic-disability-in-experimental-autoimmune-encephalomyelitis-by-altering-the-composition-of-central-nervous-system-infiltrating-cells-but-is-dispensable-for-disease-induction
#18
Patrick C Duncker, Joshua S Stoolman, Amanda K Huber, Benjamin M Segal
GM-CSF has been portrayed as a critical cytokine in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and, ostensibly, in multiple sclerosis. C57BL/6 mice deficient in GM-CSF are resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 The mechanism of action of GM-CSF in EAE is poorly understood. In this study, we show that GM-CSF augments the accumulation of MOG35-55-specific T cells in the skin draining lymph nodes of primed mice, but it is not required for the development of encephalitogenic T cells...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29285951/seifem-2017-from-real-life-to-an-agreement-on-the-use-of-granulocyte-transfusions-and-colony-stimulating-factors-for-prophylaxis-and-treatment-of-infectious-complications-in-patients-with-hematologic-malignant-disorders
#19
Alessandro Busca, Simone Cesaro, Luciana Teofili, Mario Delia, Chiara Cattaneo, Marianna Criscuolo, Francesco Marchesi, Nicola Stefano Fracchiolla, Caterina Giovanna Valentini, Francesca Farina, Roberta Di Blasi, Lucia Prezioso, Angelica Spolzino, Anna Candoni, Maria Ilaria Del Principe, Luisa Verga, Annamaria Nosari, Franco Aversa, Livio Pagano
The rapid spread of severe infections mainly due to resistant pathogens, justifies the search for therapies aiming to restore immune functions severely compromised in patients with hematologic malignancies. Areas covered: The present review summarizes the current knowledge on the role of granulocyte transfusions and colony-stimulating factors as treatment strategy for hematologic patients with serious infectious complications. In addition, a survey among 21 hematologic centers, to evaluate the clinical practice for the use of G-CSF originator and biosimilars was performed...
December 29, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29284508/inflammatory-dysregulation-of-monocytes-in-pediatric-patients-with-obsessive-compulsive-disorder
#20
Natalia Rodríguez, Astrid Morer, E Azucena González-Navarro, Carles Serra-Pages, Daniel Boloc, Teresa Torres, Susana García-Cerro, Sergi Mas, Patricia Gassó, Luisa Lázaro
BACKGROUND: Although the exact etiology of obsessive-compulsive disorder (OCD) is unknown, there is growing evidence of a role for immune dysregulation in the pathophysiology of the disease, especially in the innate immune system including the microglia. To test this hypothesis, we studied inflammatory markers in monocytes from pediatric patients with OCD and from healthy controls. METHODS: We determined the percentages of total monocytes, CD16+ monocytes, and classical (CD14highCD16-), intermediate (CD14highCD16low), and non-classical (CD14lowCD16high) monocyte subsets in 102 patients with early-onset OCD and in 47 healthy controls...
December 28, 2017: Journal of Neuroinflammation
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