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T cell RNaseq

Gottfried Martin, David Conrad, Bertan Cakir, Günther Schlunck, Hansjürgen T Agostini
PURPOSE: Retinal vein occlusion (RVO) has been investigated in several laser-induced animal models using pigs, rabbits and rats. However, laser-induced RVO has been rarely reported in mice, despite the impressive number of available mutants, ease of handling and cost effectiveness. The aim of this study was to further assess the feasibility of a RVO mouse model for gene expression analysis and its possible use to investigate effects of hypoxia. METHODS: C57Bl/6J mice were injected with eosin Y for photo-sensitization...
2018: PloS One
Thomas W Hopwood, Sarah Hall, Nicola Begley, Ruth Forman, Sheila Brown, Ryan Vonslow, Ben Saer, Matthew C Little, Emma A Murphy, Rebecca J Hurst, David W Ray, Andrew S MacDonald, Andy Brass, David A Bechtold, Julie E Gibbs, Andrew S Loudon, Kathryn J Else
Resistance to the intestinal parasitic helminth Trichuris muris requires T-helper 2 (TH 2) cellular and associated IgG1 responses, with expulsion typically taking up to 4 weeks in mice. Here, we show that the time-of-day of the initial infection affects efficiency of worm expulsion, with strong TH 2 bias and early expulsion in morning-infected mice. Conversely, mice infected at the start of the night show delayed resistance to infection, and this is associated with feeding-driven metabolic cues, such that feeding restriction to the day-time in normally nocturnal-feeding mice disrupts parasitic expulsion kinetics...
February 28, 2018: Scientific Reports
Zhongfang Wang, Lingyan Zhu, Thi H O Nguyen, Yanmin Wan, Sneha Sant, Sergio M Quiñones-Parra, Jeremy Chase Crawford, Auda A Eltahla, Simone Rizzetto, Rowena A Bull, Chenli Qiu, Marios Koutsakos, E Bridie Clemens, Liyen Loh, Tianyue Chen, Lu Liu, Pengxing Cao, Yanqin Ren, Lukasz Kedzierski, Tom Kotsimbos, James M McCaw, Nicole L La Gruta, Stephen J Turner, Allen C Cheng, Fabio Luciani, Xiaoyan Zhang, Peter C Doherty, Paul G Thomas, Jianqing Xu, Katherine Kedzierska
Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8+ T-cell profiles from patients hospitalized with avian H7N9, seasonal IAV, and influenza vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38+ HLA-DR+ PD-1+ CD8+ T cells, whereas the prolonged persistence of this set is found in ultimately fatal cases. Single-cell T cell receptor (TCR)-αβ analyses of activated CD38+ HLA-DR+ CD8+ T cells show similar TCRαβ diversity but differential clonal expansion kinetics in surviving and fatal H7N9 patients...
February 26, 2018: Nature Communications
Huseini Kagdi, Maria Antonietta Demontis, Juan Carlos Ramos, Graham P Taylor
Adult T-cell leukaemia/lymphoma (ATL) arises from chronic non-malignant human T lymphotropic virus type-1 (HTLV-1) infection which is characterized by high plasma pro-inflammatory cytokines whereas ATL is characterized by high plasma anti-inflammatory (IL-10) concentrations. The poor prognosis of ATL is partly ascribed to disease-associated immune suppression. ATL cells have a CD4+CCR4+CD26-CD7- immunophenotype but infected cells with this immunophenotype ('ATL-like' cells) are also present in non-malignant HTLV-1 infection...
February 14, 2018: PLoS Pathogens
Katherine A Green, Jason M Franasiak, Marie D Werner, Xin Tao, Jessica N Landis, Richard T Scott, Nathan R Treff
OBJECTIVE: To compare the transcriptome of cumulus cells associated with a euploid embryo that resulted in live birth with that of a sibling euploid embryo without sustained implantation. DESIGN: Paired analysis. SETTING: Academic institution. PATIENT(S): Couples undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection with preimplantation genetic screening with female age ≤42 years and normal ovarian reserve...
February 7, 2018: Fertility and Sterility
David Chiang, Xintong Chen, Stacie M Jones, Robert A Wood, Scott H Sicherer, A Wesley Burks, Donald Y M Leung, Charuta Agashe, Alexander Grishin, Peter Dawson, Wendy F Davidson, Leah Newman, Robert Sebra, Miriam Merad, Hugh A Sampson, Bojan Losic, M Cecilia Berin
BACKGROUND: The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood. OBJECTIVES: Our objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of individuals with and without peanut allergy (PA). METHODS: We obtained samples from PA individuals, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (CoFAR6)...
January 30, 2018: Journal of Allergy and Clinical Immunology
Cassidy L Bland, Christina N Byrne-Hoffman, Audry Fernandez, Stephanie L Rellick, Wentao Deng, David J Klinke
While recent clinical studies demonstrate the promise of cancer immunotherapy, a barrier for broadening the clinical benefit is identifying how tumors locally suppress cytotoxic immunity. As an emerging mode of intercellular communication, exosomes secreted by malignant cells can deliver a complex payload of coding and non-coding RNA to cells within the tumor microenvironment. Here, we quantified the RNA pay-load within tumor-derived exosomes and the resulting dynamic transcriptomic response to cytotoxic T cells upon exosome delivery to better understand how tumor-derived exosomes can alter immune cell function...
February 5, 2018: FEBS Journal
Anne T Mai, Wei Lue Tong, Yaping N Tu, George Blanck
Renal cell carcinoma exome-derived, V(D)J recombination reads had an elevated presence and variability, for both TcR-α and β, when compared to marginal tissue, reflecting an opportunity to assess tumor immunogenicity by comparison with marginal tissue T-cells. PD-1, PD-L2, CTLA4, and FOXP3, all of which are implicated in the evasion of an anti-tumor immune response, had a significantly higher expression for samples representing co-detection of productive TcR-⍺ and -β recombination reads. Samples representing tumors with productive TcR-α recombination reads but no detectable, productive TcR-β recombination reads, reflected a 20% survival advantage, and RNASeq data indicated an intermediate level of immune checkpoint gene expression for those samples...
January 18, 2018: International Immunology
Artur Mezheyeuski, Christian Holst Bergsland, Max Backman, Dijana Djureinovic, Tobias Sjöblom, Jarle Bruun, Patrick Micke
Semiquantitative assessment of immune markers by immunohistochemistry (IHC) has significant limitations for describing the diversity of the immune response in cancer. Therefore we evaluated a fluorescence-based multiplexed IHC method in combination with a multispectral imaging system to quantify immune infiltrates in situ in the environment of non-small cell lung cancer (NSCLC). A tissue microarray including 57 non-small cell lung cancer (NSCLC) cases was stained with antibodies to CD8, CD20, CD4, FOXP3, CD45RO and for pan-cytokeratin and immune cells were quantified in epithelial and stroma compartments...
December 27, 2017: Journal of Pathology
Sunil Bhakta, Lisa M Crocker, Yvonne Chen, Meredith Hazen, Melissa M Schutten, Dongwei Li, Coenraad Kuijl, Rachana Ohri, Fiona Zhong, Kirsten Achilles Poon, Mary Ann T Go, Eric Cheng, Robert Piskol, Ron Firestein, Aimee Fourie-O'Donohue, Katherine R Kozak, Helga Raab, Jo-Anne Hongo, Deepak Sampath, Mark S Dennis, Richard H Scheller, Paul Polakis, Jagath R Junutula
Luminal A (hormone receptor-positive) breast cancer constitutes 70% of total breast cancer patients. In an attempt to develop a targeted therapeutic for this cancer indication, we have identified and characterized Glial cell line-Derived Neurotrophic Factor (GDNF) Family Receptor Alpha 1 (GFRA1) antibody-drug conjugates (ADC) using a cleavable valine-citrulline-MMAE (vcMMAE) linker-payload. RNAseq and immunohistochemistry analysis confirmed the abundant expression of GFRA1 in luminal A breast cancer tissues, while minimal or no expression was observed in most normal tissues...
December 27, 2017: Molecular Cancer Therapeutics
Henrika Jodeleit, Pia Palamides, Florian Beigel, Thomas Mueller, Eckhard Wolf, Matthias Siebeck, Roswitha Gropp
BACKGROUND: Ulcerative colitis (UC) is a highly progressive inflammatory disease that requires the interaction of epithelial, immune, endothelial and muscle cells and fibroblasts. Previous studies suggested two inflammatory conditions in UC-patients: 'acute' and 'remodeling' and that the design of a disease network might improve the understanding of the inflammatory processes. The objective of the study was to design and validate a disease network in the NOD-SCID IL2rγnull (NSG)-UC mouse model to get a better understanding of the inflammatory processes...
December 28, 2017: Journal of Translational Medicine
Matthew A Summers, Thusitha Rupasinghe, Emily R Vasiljevski, Frances J Evesson, Kathy Mikulec, Lauren Peacock, Kate G R Quinlan, Sandra T Cooper, Ute Roessner, David A Stevenson, David G Little, Aaron Schindeler
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with complex symptomology. In addition to a predisposition to tumors, children with NF1 can present with reduced muscle mass, global muscle weakness, and impaired motor skills, which can have a significant impact on quality of life. Genetic mouse models have shown a lipid storage disease phenotype may underlie muscle weakness in NF1. Herein we confirm that biopsy specimens from six individuals with NF1 similarly manifest features of a lipid storage myopathy, with marked accumulation of intramyocellular lipid, fibrosis, and mononuclear cell infiltrates...
February 15, 2018: Human Molecular Genetics
Mahmood Y Bilal, Svetlana Dambaeva, Joanne Kwak-Kim, Alice Gilman-Sachs, Kenneth D Beaman
Iodine is an essential element required for the function of all organ systems. Although the importance of iodine in thyroid hormone synthesis and reproduction is well known, its direct effects on the immune system are elusive. Human leukocytes expressed mRNA of iodide transporters (NIS and PENDRIN) and thyroid-related proteins [thyroglobulin (TG) and thyroid peroxidase (TPO)]. The mRNA levels of PENDRIN and TPO were increased whereas TG transcripts were decreased post leukocyte activation. Flow cytometric analysis revealed that both PENDRIN and NIS were expressed on the surface of leukocyte subsets with the highest expression occurring on monocytes and granulocytes...
2017: Frontiers in Immunology
Marlies Schrevel, Willem E Corver, Margit E Vegter, Natalja T Ter Haar, Enno J Dreef, Jogchum J Beltman, Gemma Kenter, Tjalling Bosse, Cornelis D de Kroon, Ekaterina S Jordanova
Background: L1 cell adhesion molecule (L1CAM) has been shown to be a prognostic marker in various cancer types, and has been suggested to play a role in epithelial mesenchymal transition (EMT). Here, we determined the prognostic significance of L1CAM in cervical cancer and its association with vimentin expression on tumor cells, indicative of EMT. Methods: Formalin-fixed, paraffin-embedded primary tumor samples from 372 cervical cancer patients were collected for immunohistochemical analysis of L1CAM expression...
October 20, 2017: Oncotarget
Rachel A Rusk, Mitchell V Palmer, W Ray Waters, Jodi L McGill
Bovine γδ T cells are amongst the first cells to accumulate at the site of Mycobacterium bovis infection; however, their role in the developing lesion remains unclear. We utilized transcriptomics analysis, in situ hybridization, and a macrophage/γδ T cell co-culture system to elucidate the role of γδ T cells in local immunity to M. bovis infection. Transcriptomics analysis revealed that γδ T cells upregulated expression of several novel, immune-associated genes in response to stimulation with M. bovis antigen...
December 2017: Veterinary Immunology and Immunopathology
Etienne G J Danchin, Laetitia Perfus-Barbeoch, Corinne Rancurel, Peter Thorpe, Martine Da Rocha, Simon Bajew, Roy Neilson, Elena Sokolova Guzeeva, Corinne Da Silva, Julie Guy, Karine Labadie, Daniel Esmenjaud, Johannes Helder, John T Jones, Sebastian Eves-van den Akker
Nematodes have evolved the ability to parasitize plants on at least four independent occasions, with plant parasites present in Clades 1, 2, 10 and 12 of the phylum. In the case of Clades 10 and 12, horizontal gene transfer of plant cell wall degrading enzymes from bacteria and fungi has been implicated in the evolution of plant parasitism. We have used ribonucleic acid sequencing (RNAseq) to generate reference transcriptomes for two economically important nematode species, Xiphinema index and Longidorus elongatus, representative of two genera within the early-branching Clade 2 of the phylum Nematoda...
October 23, 2017: Genes
Bryan Nicol, Marion Salou, Isabel Vogel, Alexandra Garcia, Emilie Dugast, Jeremy Morille, Stéphanie Kilens, Eric Charpentier, Audrey Donnart, Steven Nedellec, Marylène Jacq-Foucher, Fabienne Le Frère, Sandrine Wiertlewski, Arnaud Bourreille, Sophie Brouard, Laure Michel, Laurent David, Pierre-Antoine Gourraud, Nicolas Degauque, Arnaud B Nicot, Laureline Berthelot, David-Axel Laplaud
Several lines of evidence support a key role for CD8(+) T cells in central nervous system tissue damage of patients with multiple sclerosis. However, the precise phenotype of the circulating CD8(+) T cells that may be recruited from the peripheral blood to invade the CNS remains largely undefined to date. It has been suggested that IL-17 secreting CD8 (Tc17) T cells may be involved, and in humans these cells are characterized by the expression of CD161. We focused our study on a unique and recently described subset of CD8 T cells characterized by an intermediate expression of CD161 as its role in neuroinflammation has not been investigated to date...
October 17, 2017: Journal of Autoimmunity
T Klymenko, Q Gu, I Herbert, A Stevenson, V Iliev, G Watkins, C Pollock, R Bhatia, K Cuschieri, P Herzyk, D Gatherer, S V Graham
The human papillomavirus (HPV) replication cycle is tightly linked to epithelial cell differentiation. To examine HPV-associated changes in the keratinocyte transcriptome, RNAs isolated from undifferentiated and differentiated cell populations of normal, spontaneously immortalised, keratinocytes (NIKS), and NIKS stably transfected with HPV16 episomal genomes (NIKS16), were compared using RNASeq. HPV16 infection altered expression of 2862 cellular genes. Next, to elucidate the role of keratinocyte gene expression in late events during the viral life cycle, RNASeq was carried out on triplicate differentiated populations of NIKS (uninfected) and NIKS16 (infected)...
October 11, 2017: Journal of Virology
Robert King, Martin Urban, Rebecca P Lauder, Nichola Hawkins, Matthew Evans, Amy Plummer, Kirstie Halsey, Alison Lovegrove, Kim Hammond-Kosack, Jason J Rudd
Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants. However, the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form. During a random T-DNA mutagenesis screen performed on the pleomorphic wheat (Triticum aestivum) pathogen Zymoseptoria tritici, we acquired a mutant unable to extend hyphae specifically when on solid surfaces. In contrast "yeast-like" growth, and all other growth forms, were unaffected...
October 2017: PLoS Pathogens
James T Lynch, Urszula M Polanska, Oona Delpuech, Urs Hancox, Antonio G Trinidad, Filippos Michopoulos, Carol Lenaghan, Robert McEwen, James Bradford, Radek Polanski, Rebecca Ellston, Alvaro Avivar-Valderas, James Pilling, Anna Staniszewska, Marie Cumberbatch, Susan E Critchlow, Francisco Cruzalegui, Simon T Barry
Purpose: PTEN-null tumors become dependent on the PI3Kβ isoform and can be targeted by molecules such as the selective PI3Kβ inhibitor AZD8186. However, beyond the modulation of the canonical PI3K pathway, the consequences of inhibiting PI3Kβ are poorly defined. Experimental Design: To determine the broader impact of AZD8186 in PTEN-null tumors, we performed a genome-wide RNA-seq analysis of PTEN-null triple-negative breast tumor xenografts treated with AZD8186. Mechanistic consequences of AZD8186 treatment were examined across a number of PTEN-null cell lines and tumor models...
December 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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