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https://www.readbyqxmd.com/read/29784760/formation-of-the-intrathymic-dendritic-cell-pool-requires-ccl21-mediated-recruitment-of-ccr7-progenitors-to-the-thymus
#1
Emilie J Cosway, Izumi Ohigashi, Karin Schauble, Sonia M Parnell, William E Jenkinson, Sanjiv Luther, Yousuke Takahama, Graham Anderson
During αβ T cell development in the thymus, migration of newly selected CD4+ and CD8+ thymocytes into medullary areas enables tolerance mechanisms to purge the newly selected αβ TCR repertoire of autoreactive specificities. Thymic dendritic cells (DC) play key roles in this process and consist of three distinct subsets that differ in their developmental origins. Thus, plasmacytoid DC and Sirpα+ conventional DC type 2 are extrathymically derived and enter into the thymus via their respective expression of the chemokine receptors CCR9 and CCR2...
May 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29783997/graft-protective-effect-and-induction-of-cd4-foxp3-cell-by-thrombomodulin-on-allograft-arteriosclerosis-in-mice
#2
Enzhi Yin, Shigefumi Matsuyama, Masateru Uchiyama, Kento Kawai, Masanori Niimi
BACKGROUND: Thrombomodulin (TM) is a promising therapeutic natural anti-coagulant, which exerts the effects to control disseminated intravascular coagulation. However, little is known whether TM on micro-vessels could play an important role in the regulation of intimal hyperplasia. We investigated the vessel-protective effect of TM in the survival of fully major histocompatibility complex (MHC)-mismatched murine cardiac allograft transplantation. METHODS: CBA recipients transplanted with a C57BL/6 heart received intraperitoneal administration of normal saline or 0...
May 21, 2018: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/29783708/following-acute-encephalitis-semliki-forest-virus-is-undetectable-in-the-brain-by-infectivity-assays-but-functional-virus-rna-capable-of-generating-infectious-virus-persists-for-life
#3
Rennos Fragkoudis, Catherine M Dixon-Ballany, Adrian K Zagrajek, Lukasz Kedzierski, John K Fazakerley
Alphaviruses are mosquito-transmitted RNA viruses which generally cause acute disease including mild febrile illness, rash, arthralgia, myalgia and more severely, encephalitis. In the mouse, peripheral infection with Semliki Forest virus (SFV) results in encephalitis. With non-virulent strains, infectious virus is detectable in the brain, by standard infectivity assays, for around ten days. As we have shown previously, in severe combined immunodeficient (SCID) mice, infectious virus is detectable for months in the brain...
May 18, 2018: Viruses
https://www.readbyqxmd.com/read/29782535/mycobacterium-tuberculosis-specific-cd4-and-cd8-t-cells-differ-in-their-capacity-to-recognize-infected-macrophages
#4
Jason D Yang, Daniel Mott, Rujapak Sutiwisesak, Yu-Jung Lu, Fiona Raso, Britni Stowell, Greg Hunter Babunovic, Jinhee Lee, Steve M Carpenter, Sing Sing Way, Sarah M Fortune, Samuel M Behar
Containment of Mycobacterium tuberculosis (Mtb) infection requires T cell recognition of infected macrophages. Mtb has evolved to tolerate, evade, and subvert host immunity. Despite a vigorous and sustained CD8+ T cell response during Mtb infection, CD8+ T cells make limited contribution to protection. Here, we ask whether the ability of Mtb-specific T cells to restrict Mtb growth is related to their capacity to recognize Mtb-infected macrophages. We derived CD8+ T cell lines that recognized the Mtb immunodominant epitope TB10...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782520/polymorphic-sites-preferentially-avoid-co-evolving-residues-in-mhc-class-i-proteins
#5
Linda Dib, Nicolas Salamin, David Gfeller
Major histocompatibility complex class I (MHC-I) molecules are critical to adaptive immune defence mechanisms in vertebrate species and are encoded by highly polymorphic genes. Polymorphic sites are located close to the ligand-binding groove and entail MHC-I alleles with distinct binding specificities. Some efforts have been made to investigate the relationship between polymorphism and protein stability. However, less is known about the relationship between polymorphism and MHC-I co-evolutionary constraints...
May 21, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29778202/porcine-monocyte-derived-dendritic-cells-can-be-differentially-activated-by-vesicular-stomatitis-virus-and-its-matrix-protein-mutants
#6
Guoyan Sun, Xinkui Fang, Hao Wu, Xinchu Zhou, Yong Ke, Tao Sun
Vesicular stomatitis virus (VSV) can cause serious vesicular lesions in pigs, and the matrix (M) protein is its predominant virulence factor. Dendritic cells (DCs) act as the bridge between innate and adaptive immune responses. However, the susceptibility of porcine DCs to VSV infection and the role of M protein in modulating the function of infected DCs are still poorly defined. Thus, this study aimed to determine the ability of virulent wild-type VSV(wtVSV) and two attenuated M protein variants (VSVΔM51 and VSVMT ) to induce maturation of porcine monocyte-derived DCs (MoDCs) in vitro...
June 2018: Veterinary Microbiology
https://www.readbyqxmd.com/read/29778085/braf-and-mek-inhibitor-therapy-eliminates-nestin-expressing-melanoma-cells-in-human-tumors
#7
Deon B Doxie, Allison R Greenplate, Jocelyn S Gandelman, Kirsten E Diggins, Caroline E Roe, Kimberly B Dahlman, Jeffrey A Sosman, Mark C Kelley, Jonathan M Irish
Little is known about the in vivo impacts of targeted therapy on melanoma cell abundance and protein expression. Here, 21 antibodies were added to an established melanoma mass cytometry panel to measure 32 cellular features, distinguish malignant cells, and characterize dabrafenib and trametinib responses in BRAFV 600mut melanoma. Tumor cells were biopsied before neoadjuvant therapy and compared to cells surgically resected from the same site after 4 weeks of therapy. Approximately 50,000 cells per tumor were characterized by mass cytometry and computational tools t-SNE/viSNE, FlowSOM, and MEM...
May 19, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29777029/cd4-t-cell-affinity-diversity-is-equally-maintained-during-acute-and-chronic-infection
#8
Rakieb Andargachew, Ryan J Martinez, Elizabeth M Kolawole, Brian D Evavold
TCR affinity for peptide MHC dictates the functional efficiency of T cells and their propensity to differentiate into effectors and form memory. However, in the context of chronic infections, it is unclear what the overall profile of TCR affinity for Ag is and if it differs from acute infections. Using the comprehensive affinity analysis provided by the two-dimensional micropipette adhesion frequency assay and the common indirect affinity evaluation methods of MHC class II tetramer and functional avidity, we tracked IAb GP61-80 -specific cells in the mouse model of acute (Armstrong) and chronic (clone 13) lymphocytic choriomeningitis virus infection...
May 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29776607/differentiation-of-equine-bone-marrow-derived-mesenchymal-stem-cells-increases-the-expression-of-immunogenic-genes
#9
Laura Barrachina, Ana Rosa Remacha, Antonio Romero, Pilar Zaragoza, Francisco José Vázquez, Clementina Rodellar
Mesenchymal stem cells (MSCs) are a promising treatment for equine musculoskeletal injuries because of their ability to regulate the inflammation and to differentiate into other cell types. Since interest in allogeneic therapy is rising, concerns about MSC immunogenicity need to be addressed. Differentiated MSCs from several species increase their expression of immunogenic molecules and induce alloresponses, but equine MSC immunogenic profile after differentiation has not been reported. Therefore, the aim of this study was to assess the gene expression of immunogenic markers in tri-lineage differentiated equine bone marrow derived MSCs (eBM-MSCs)...
June 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29776409/calcitriol-downregulates-fibroblast-growth-factor-receptor-1-through-histone-deacetylase-activation-in-hl-1-atrial-myocytes
#10
Ting-Wei Lee, Ting-I Lee, Yung-Kuo Lin, Yu-Hsun Kao, Yi-Jen Chen
BACKGROUND: Fibroblast growth factor (FGF)-2 plays a crucial role in the pathophysiology of cardiovascular diseases (CVDs). FGF-2 was reported to induce cardiac hypertrophy through activation of FGF receptor 1 (FGFR1). Multiple laboratory findings indicate that calcitriol may be a potential treatment for CVDs. In this study, we attempted to investigate whether calcitriol regulates FGFR1 expression to modulate the effects of FGF-2 signaling in cardiac myocytes and explored the potential regulatory mechanism...
May 18, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29776088/how-nonuniform-contact-profiles-of-t-cell-receptors-modulate-thymic-selection-outcomes
#11
Hanrong Chen, Arup K Chakraborty, Mehran Kardar
T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775222/abca1-inhibits-pdgf-induced-proliferation-and-migration-of-rat-airway-smooth-muscle-cell-through-blocking-tlr2-nf-%C3%AE%C2%BAb-nfatc1-signaling
#12
Wei Cheng, Kun Yan, Yanni Chen, Wen Zhang, Zongzheng Ji, Chengxue Dang
Airway remodeling is a key feature of asthma, characterized by abnormal proliferation and migration of airway smooth muscle cells (ASMCs). ABCA1, a member of the ATP-binding cassette family of active transporters, plays an essential role in the progression of lung diseases. However, the contributions of ABCA1 in ASMCs remain to be explored. The purpose of the present study was to investigate the functional role and potential molecular mechanism of ABCA1 in platelet derived growth factor (PDGF)-induced primary rat ASMC proliferation and migration...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29772523/mhc-b-haplotypes-impact-susceptibility-and-resistance-to-rsv-a-infection
#13
Vishwa Mohini Khare, Vishesh Kumar Saxena, Alka Tomar, Karam Pal Singh, Kunwar Bahadur Singh, Amit Kumar Tiwari
We investigated the impact of haplotype of major histocompatibility complex (MHC)-B on the outcome of infection of Synthetic Dam Line (SDL) broiler strain with Rous Sarcoma Virus (RSV). Genomic analysis of MHC-B haplotypes, revealed a total of 12 known standard haplotypes that constituted to twenty-five different genotypes and one new haplotype of 217 bp size, designated BX . The inoculation of RSV-A in SDL chicks resulted in the development of tumors of progressive or regressive phenotypes with varying tumor profile index (TPI)...
June 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/29772011/induction-of-influenza-specific-local-cd8-t-cells-in-the-respiratory-tract-after-aerosol-delivery-of-vaccine-antigen-or-virus-in-the-babraham-inbred-pig
#14
Katie Tungatt, Garry Dolton, Sophie B Morgan, Meriem Attaf, Anna Fuller, Thomas Whalley, Johanneke D Hemmink, Emily Porter, Barbara Szomolay, Maria Montoya, John A Hammond, John J Miles, David K Cole, Alain Townsend, Mick Bailey, Pierre J Rizkallah, Bryan Charleston, Elma Tchilian, Andrew K Sewell
There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29771935/cell-iron-status-influences-macrophage-polarization
#15
Rafiou Agoro, Meriem Taleb, Valerie F J Quesniaux, Catherine Mura
Macrophages play crucial roles in innate immune response and in the priming of adaptive immunity, and are characterized by their phenotypic heterogeneity and plasticity. Reprogramming intracellular metabolism in response to microenvironmental signals is required for M1/M2 macrophage polarization and function. Here we assessed the influence of iron on the polarization of the immune response in vivo and in vitro. Iron-enriched diet increased M2 marker Arg1 and Ym1 expression in liver and peritoneal macrophages, while iron deficiency decreased Arg1 expression...
2018: PloS One
https://www.readbyqxmd.com/read/29771428/ampk-regulates-energy-metabolism-through-the-sirt1-signaling-pathway-to-improve-myocardial-hypertrophy
#16
H-W Dong, L-F Zhang, S-L Bao
OBJECTIVE: We investigated the correlations of adenosine monophosphate-activated protein kinase (AMPK), Silence information regulator 1 (SIRT1) and energy metabolism with myocardial hypertrophy. MATERIALS AND METHODS: Myocardial hypertrophy experimental model was established via transverse aortic constriction (TAC)-induced myocardial hypertrophy and phenylephrine (PE)-induced hypertrophic myocardial cell culture. After activation of AMPK, the messenger ribonucleic acid (mRNA) expressions in myocardial tissue- and myocardial cell hypertrophy-related genes, atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC), were detected...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29769526/a-whole-genome-sequence-study-identifies-genetic-risk-factors-for-neuromyelitis-optica
#17
Karol Estrada, Christopher W Whelan, Fengmei Zhao, Paola Bronson, Robert E Handsaker, Chao Sun, John P Carulli, Tim Harris, Richard M Ransohoff, Steven A McCarroll, Aaron G Day-Williams, Benjamin M Greenberg, Daniel G MacArthur
Neuromyelitis optica (NMO) is a rare autoimmune disease that affects the optic nerve and spinal cord. Most NMO patients ( > 70%) are seropositive for circulating autoantibodies against aquaporin 4 (NMO-IgG+). Here, we meta-analyze whole-genome sequences from 86 NMO cases and 460 controls with genome-wide SNP array from 129 NMO cases and 784 controls to test for association with SNPs and copy number variation (total N = 215 NMO cases, 1244 controls). We identify two independent signals in the major histocompatibility complex (MHC) region associated with NMO-IgG+, one of which may be explained by structural variation in the complement component 4 genes...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769317/lysophospholipids-induce-innate-immune-transdifferentiation-of-endothelial-cells-resulting-in-prolonged-endothelial-activation
#18
Xinyuan Li, Luqiao Wang, Pu Fang, Yu Sun, Xiaohua Jiang, Hong Wang, Xiao-Feng Yang
Innate immune cells express danger-associated molecular pattern (DAMP) receptors, T-cell co-stimulation/co-inhibition receptors, and the major histocompatibility complex II (MHC-II). We have recently proposed that endothelial cells can serve as innate immune cells, but the molecular mechanisms involved still await discovery. Here, we investigated whether human aortic endothelial cells (HAECs) could be transdifferentiated into innate immune cells by exposing them to hyperlipidemia-upregulated DAMP molecules, i...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29769311/tumor-associated-calreticulin-variants-functionally-compromise-the-peptide-loading-complex-and-impair-its-recruitment-of-mhc-i
#19
Najla Arshad, Peter Cresswell
Major histocompatibility complex-I-β2 m dimers (MHC-I) bind peptides derived from intracellular proteins, enabling the immune system to distinguish between normal cells and those expressing pathogen-derived or mutant proteins. The peptides bind to MHC-I in the endoplasmic reticulum (ER), and this binding is facilitated by the peptide-loading complex (PLC), which contains calreticulin (CRT). CRT associates with MHC-I via a conserved glycan present on MHC-I and recruits it to the PLC for peptide binding. Somatic frameshift mutations in CRT (CRT-FS) drive the proliferation of a subset of myeloproliferative neoplasms (MPNs), which are chronic blood tumors...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29768981/a-scalable-pipeline-for-high-throughput-flow-cytometry
#20
Aaron C Wilson, Ioannis K Moutsatsos, Gary Yu, Javier J Pineda, Yan Feng, Douglas S Auld
Flow cytometry (FC) provides high-content data for a variety of applications, including phenotypic analysis of cell surface and intracellular markers, characterization of cell supernatant or lysates, and gene expression analysis. Historically, sample preparation, acquisition, and analysis have presented as a bottleneck for running such types of assays at scale. This article will outline the solutions that have been implemented at Novartis which have allowed high-throughput FC to be successfully conducted and analyzed for a variety of cell-based assays...
May 1, 2018: SLAS Discovery
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