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T cell fibroblast

Young C Shin, Georg F Bischof, William A Lauer, Lucas Gonzalez-Nieto, Eva G Rakasz, Gregory M Hendricks, David I Watkins, Mauricio A Martins, Ronald C Desrosiers
The properties of the human immunodeficiency virus (HIV) pose serious difficulties for the development of an effective prophylactic vaccine. Here we describe the construction and characterization of recombinant (r), replication-competent forms of rhesus monkey rhadinovirus (RRV), a gamma-2 herpesvirus, containing a near-full-length (nfl) genome of the simian immunodeficiency virus (SIV). A 306-nucleotide deletion in the pol gene rendered this nfl genome replication-incompetent as a consequence of deletion of the active site of the essential reverse transcriptase enzyme...
June 18, 2018: PLoS Pathogens
Delfina Costa, Roberta Venè, Roberto Benelli, Emanuele Romairone, Stefano Scabini, Silvia Catellani, Barbara Rebesco, Luca Mastracci, Federica Grillo, Simona Minghelli, Fabrizio Loiacono, Maria Raffaella Zocchi, Alessandro Poggi
Mesenchymal stromal cells (MSC) present in the tumor microenvironment [usually named tumor-associated fibroblasts (TAF)] can exert immunosuppressive effects on T and natural killer (NK) lymphocytes, favoring tumor immune escape. We have analyzed this mechanism in colorectal carcinoma (CRC) and found that co-culture of NK cells with TAF can prevent the IL-2-mediated NKG2D upregulation. This leads to the impairment of NKG2D-mediated recognition of CRC cells, sparing the NK cell activation through DNAM1 or FcγRIIIA (CD16)...
2018: Frontiers in Immunology
Ellen J Beswick, Carl Grim, Abinav Singh, Jose E Aguirre, Marissa Tafoya, Suimin Qiu, Gerhard Rogler, Rohini McKee, Von Samedi, Thomas Y Ma, Victor E Reyes, Don W Powell, Irina V Pinchuk
Background and Aims: The role of programmed cell death protein 1 (PD-1) and its ligands in the dysregulation of T helper immune responses observed in the inflammatory bowel disease (IBD) is unclear. Recently, a novel concept emerged that CD90+ colonic (myo)fibroblasts (CMFs), also known as stromal cells, act as immunosuppressors, and are among the key regulators of acute and chronic inflammation. The objective of this study was to determine if the level of the PD-1 ligands is changed in the IBD inflamed colonic mucosa and to test the hypothesis that changes in IBD-CMF-mediated PD-1 ligand-linked immunosuppression is a mechanism promoting the dysregulation of Th1 cell responses...
2018: Frontiers in Immunology
Bharti Garg, Bhuwan Giri, Shrey Modi, Vrishketan Sethi, Iris Castro, Oliver Umland, Yuguang Ban, Shweta Lavania, Rajinder Dawra, Sulagna Banerjee, Selwyn Vickers, Nipun B Merchant, Steven Xi Chen, Eli Gilboa, Sundaram Ramakrishnan, Ashok Saluja, Vikas Dudeja
BACKGROUND & AIMS: Immunotherapies are ineffective against pancreatic cancer. We investigated whether the activity of nuclear factor (NF)κB in pancreatic stromal cells contributes to an environment that suppresses anti-tumor immune response. METHODS: Pancreata of C57BL/6 or Rag1-/- mice were given pancreatic injections of a combination of KrasG12D/+; Trp53 R172H/+; Pdx-1cre (KPC) pancreatic cancer cells and pancreatic stellate cells (PSCs) extracted from C57BL/6 (control) or mice with disruption of the gene encoding the NFkB p50 subunit (Nfkb1 or p50-/- mice)...
June 14, 2018: Gastroenterology
E Mammadova-Bach, T Rupp, C Spenlé, I Jivkov, P Shankaranarayanan, A Klein, L Pisarsky, A Méchine-Neuville, G Cremel, M Kedinger, O De Wever, N Ambartsumian, S Robine, E Pencreach, D Guenot, P Simon-Assmann, J G Goetz, G Orend, O Lefebvre
Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumor-stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth. The underlying mechanism involves attraction of carcinoma-associated fibroblasts by LMα1, VEGFA expression triggered by the complex integrin α2β1-CXCR4 and binding of VEGFA to LM-111, which in turn promotes angiogenesis, tumor cell survival and proliferation...
June 15, 2018: Biology of the Cell
Lauren A Callender, Elizabeth C Carroll, Emilia A Bober, Sian M Henson
The impact of cellular senescence during ageing is well established, however senescence is now recognised to play a role in a variety of age related and metabolic diseases, such as cancer, autoimmune and cardiovascular diseases. It is therefore crucial to gain a better understanding of the mechanisms that control cellular senescence. In recent years our understanding of the intimate relationship between cell metabolism, cell signalling and cellular senescence has greatly improved. In this review we discuss the differing roles of glucose and protein metabolism in both senescent fibroblast and CD8+ T-cells, and explore the impact cellular metabolism has on the senescence-associated secretory phenotype (SASP) of these cell types...
June 11, 2018: Ageing Research Reviews
Julie Jacobs, Vanessa Deschoolmeester, Karen Zwaenepoel, Tal Flieswasser, Christophe Deben, Jolien Van den Bossche, Christophe Hermans, Christian Rolfo, Marc Peeters, Olivier De Wever, Filip Lardon, Vasiliki Siozopoulou, Evelien Smits, Patrick Pauwels
Cancer-associated fibroblasts (CAFs) are involved in the proliferative and invasive behavior of colorectal cancer (CRC). Nonetheless, CAFs represent a heterogeneous population with both cancer-promoting and cancer-restraining actions, lacking specific markers to target them. Expression of the immune checkpoint molecule CD70 is normally limited to cells of the lymphoid lineage. Instead, tumor cells hijack CD70 to facilitate immune evasion by increasing the amount of suppressive regulatory T cells (Tregs). The aim of this study was to explore CD70 expression patterns in CRC, not merely focusing on the tumor cells, but also taking the tumor stromal cells into account...
2018: Oncoimmunology
Tobias Bald, Mark J Smyth
T cell exclusion from cancers is a major problem for a proportion of patients suffering poor outcomes. Two papers recently published in Nature highlight the negative role of cancer associated fibroblast TGFβ. These studies indicate that TGFβ enables T cell exclusion in a proportion of colorectal and urothelial cancers, and in the latter disease may reduce their response to anti-PD-L1 immunotherapy.
June 14, 2018: British Journal of Cancer
Cai Yanling, Liu Hongyan, Wei Xi, Crielaard Wim, Deng Dongmei
OBJECTIVE: Relacin is a synthetic molecule that targets RelA, an essential protein in a conserved bacterial stress response system. It was shown to inhibit bacterial growth. The aims of this study were to evaluate the antimicrobial effect of relacin combined with sodium hypochlorite (NaOCl) on Enterococcus faecalis biofilms and to evaluate the cytotoxicity of relacin. MATERIAL AND METHODS: 48-h E. faecalis OG1RF biofilms were treated by various concentrations of relacin in order to determine its inhibitory concentration...
June 11, 2018: Journal of Applied Oral Science: Revista FOB
Maren Leifheit-Nestler, Dieter Haffner
Fibroblast growth factor (FGF) 23 is a phosphaturic hormone primarily secreted by osteocytes to maintain phosphate and mineral homeostasis. In patients with and without chronic kidney disease, enhanced circulating FGF23 levels associate with pathologic cardiac remodeling, i.e., left ventricular hypertrophy (LVH) and myocardial fibrosis and increased cardiovascular mortality. Experimental studies demonstrate that FGF23 promotes hypertrophic growth of cardiac myocytes via FGF receptor 4-dependent activation of phospholipase Cγ/calcineurin/nuclear factor of activated T cell signaling independent of its co-receptor klotho...
2018: Frontiers in Endocrinology
Yu-Li Lin, Pei-Yun Cheng, Chiao-Li Chin, Li-Min Huang, Shr-Yu Lin, Bor-Luen Chiang
To prevent viral infection at the site of entry, mucosal vaccines are potent tools for inducing IgA secretion for defense. Because Toll-like receptor (TLR) ligands serve as strong adjuvants, two ligands that mimic the structure of mycoplasmal and bacterial lipopeptides represent interesting vaccine candidates. Pam3CSK4, a synthetic triacylated lipopeptide, interacts with TLR2/1. Because fibroblast-stimulating lipopeptide-1 (FSL-1), a synthetic diacylated lipopeptide, is recognized by TLR2/6, we targeted the potential immuno-inducibility of Pam3CSK4 and FSL-1 as adjuvants of an enterovirus 71 (EV71) mucosal vaccine...
June 8, 2018: Vaccine
S B Cele, F Odun-Ayo, O A Onyangunga, J Moodley, T Naicker
OBJECTIVE: Hepatocyte Growth Factor (HGF) plays a role in the migration and morphogenesis of different cell types and tissues. Preeclampsia (PE) is associated with deficient trophoblast invasion and placental insufficiency; hence HGF production is expected to be compromised. This study therefore aimed to immunolocalize and morphometrically analyse placental HGF in normotensive versus PE pregnancies stratified by HIV status and gestational age. STUDY DESIGN: Normotensive (N; n = 40) and preeclamptic (PE; n = 80) women were stratified by HIV status (HIV- and HIV+), and gestational age i...
June 1, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Zhenzhong Wang, Xianglong Yu, Xiaoyu Niu, Jing Yang, Yi Tang, Jingdong Hu, Youxiang Diao
The NS1protein, a nonstructural protein of Tembusu virus, plays a key role in the pathogenesis of TMUV. To research host proteins that interact with NS1 protein, the cDNA library of duck embryo fibroblasts (DEF) was successfully constructed. The recombinant plasmid, pGBKT7-NS1, was transformed into the yeast Y2H to be cloned and tested for autoactivation and toxicity. The autoactivation and toxicity test of bait showed that the yeast two hybrid test could be carried out normally. A total of 7 clones from the library were got by Yeast Two-Hybrid System, and 4 proteins, including RPS7, MORC3, GABARAPL1 and MTSS1, may be interacted with DTMUV NS1 after sequencing and blast...
June 5, 2018: Infection, Genetics and Evolution
Trivia Frazier, Stephen Lee, Annie Bowles, Julie Semon, Bruce Bunnell, Xiying Wu, Jeffrey Gimble
Adipose tissue is now recognized as a functional organ that contains cellular heterogeneity and diversity within anatomical depots. The stromal vascular fraction (SVF) of adipose contains endothelial progenitors, fibroblasts, lymphocytes, monocyte/macrophages, pericytes, pre-adipocytes, and stromal/stem cells, among others. In recent years, there has been a growing appreciation of the influence of age and gender in the field of stem cell biology. Yet few studies have evaluated the influence of biological age or sex on either SVF cell heterogeneity or immunophenotype...
June 8, 2018: Adipocyte
F Zhang, M Suzuki, I S Kim, R Kobayashi, N Hamada, F Sato, U K Bhawal
BACKGROUND AND OBJECTIVES: Disruption of transcriptional regulation is a confounding factor associated with a wide range of human inflammatory diseases. To investigate mechanistic links between transcription factor DEC1 and pathways underlying inflammation, wild-type and DEC1 knockout (KO) C57BL/6 mice were treated with Porphyromonas gingivalis (or carboxymethyl cellulose as a control) to induce periodontal inflammation. It provoked an inflammatory response within the oral environment, which showed robust variation in alveolar bone resorption and expression of inflammatory cytokines...
June 7, 2018: Journal of Periodontal Research
Raúl Jiménez-P, Carla Martín-Cortázar, Omar Kourani, Yuri Chiodo, Raul Cordoba, María Purificación Domínguez-Franjo, Juan Miguel Miguel Redondo, Teresa Iglesias, Miguel R Campanero
Tumor formation involves the acquisition of numerous capacities along the progression from a normal cell into a malignant cell, including limitless proliferation (immortalization) and anchorage-independent growth, a capacity that correlates extremely well with tumorigenesis. Great efforts have been made to uncover genes involved in tumor formation, but most genes identified participate in processes related to cell proliferation. Accordingly, therapies targeting these genes also affect the proliferation of normal cells...
June 7, 2018: Haematologica
Dragana Odobasic, Yuan Jia, Wenping Kao, Huapeng Fan, Xuemin Wei, Ran Gu, Devi Ngo, A Richard Kitching, Stephen R Holdsworth, Eric F Morand, Yuan H Yang
The effects of formyl peptide receptors (FPRs) on effector T cells and inflammation-causing tissue-resident cells are not well known. Here, we explored the effect of FPR activation on efferent T cell responses in models of rheumatoid arthritis (RA) and on the expansion of fibroblast-like synoviocytes (FLS). Compound 43 (Cpd43; FPR1/2 agonist) was administered to mice with collagen-induced arthritis (CIA) or antigen-induced arthritis (AIA) after disease onset. Joint inflammation/damage and immunity were assessed...
June 4, 2018: International Immunopharmacology
Aref Shahini, Kalyan Vydiam, Debanik Choudhury, Nika Rajabian, Thy Nguyen, Pedro Lei, Stelios T Andreadis
Skeletal muscle (SkM) regeneration relies on the activity of myogenic progenitors that reside beneath the basal lamina of myofibers. Here, we describe a protocol for the isolation of the SkM progenitors from young and old mice by exploiting their outgrowth potential from SkM explants on matrigel coated dishes in the presence of high serum, chicken embryo extract and basic fibroblast growth factor. Compared to other protocols, this method yields a higher number of myoblasts (10-20 million) by enabling the outgrowth of these cells from tissue fragments...
May 24, 2018: Stem Cell Research
Angel Ashikov, Nurulamin Abu Bakar, Xiao-Yan Wen, Marco Niemeijer, Glentino Rodrigues Pinto Osorio, Koroboshka Brand-Arzamendi, Linda Hasadsri, Hana Hansikova, Kimiyo Raymond, Dorothée Vicogne, Marleen E H Simon, Rolph Pfundt, Sharita Timal, Roel Beumers, Christophe Biot, Roel Smeets, Marjan Kersten, Karin Huijben, Peter Ta Linders, Geert van den Bogaart, Sacha A F T van Hijum, Richard Rodenburg, Lambertus P van den Heuvel, Francjan van Spronsen, Tomas Honzik, Francois Foulquier, Monique van Scherpenzeel, Dirk J Lefeber
Genomics methodologies have significantly improved elucidation of Mendelian disorders. The combination with high-throughput functional-omics technologies potentiates the identification and confirmation of causative genetic variants, especially in singleton families of recessive inheritance. In a cohort of 99 individuals with abnormal Golgi glycosylation, 47 of which being unsolved, glycomics profiling was performed of total plasma glycoproteins. Combination with whole-exome sequencing in 31 cases revealed a known genetic defect in 15 individuals...
June 5, 2018: Human Molecular Genetics
Reza B Jalili, Ruhangiz T Kilani, Yunyuan Li, Mohsen Khosravi-Maharlooie, Layla Nabai, Eddy Hsi Chun Wang, Kevin J McElwee, Aziz Ghahary
Alopecia areata (AA) is an autoimmune hair loss disease with infiltration of proinflammatory cells into hair follicles. Current therapeutic regimens are unsatisfactory mainly because of the potential for side effects and/or limited efficacy. Here we report that cultured, transduced fibroblasts, which express the immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO), can be applied to prevent hair loss in an experimental AA model. A single intraperitoneal (IP) injection of IDO-expressing primary dermal fibroblasts was given to C3H/HeJ mice at the time of AA induction...
January 1, 2018: Cell Transplantation
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