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https://www.readbyqxmd.com/read/28231426/engineering-of-anti-cd133-tri-specific-molecule-capable-of-inducing-nk-expansion-and-driving-antibody-dependent-cell-mediated-cytotoxicity-adcc
#1
Jörg U Schmohl, Martin Felices, Felix Oh, Alexander J Lenvik, Aaron M Lebeau, Jayanth Panyam, Jeffrey S Miller, Daniel A Vallera
Purpose: The selective elimination of cancer stem cells (CSCs) in tumor patients is a crucial goal because CSCs cause drug refractory relapse. To improve the current conventional bispecific immune-engager platform, a 16133 BiKE, consisting of scFvs binding FcγRIII (CD16) on NK cells and CD133 on carcinoma cells, was first synthesized and a modified IL-15 crosslinker capable of stimulating NK effector cells was introduced. Materials and Methods: DNA shuffling and ligation techniques were used to assemble and synthesize the 1615133 trispecific NK cell engager (TriKE)...
February 20, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28224212/upregulation-of-thioredoxin-1-in-activated-human-nk-cells-confers-increased-tolerance-to-oxidative-stress
#2
Kousaku Mimura, Ley-Fang Kua, Noriko Shimasaki, Kensuke Shiraishi, Shotaro Nakajima, Lim Kee Siang, Asim Shabbir, Jimmy So, Wei-Peng Yong, Koji Kono
Adoptive transfer of immune cells, such as T lymphocytes and NK cells, has potential to control cancer growth. However, this can be counteracted by immune escape mechanisms within the tumor microenvironment, including those mediated by reactive oxygen species (ROS). Here, we determined the levels of anti-oxidant molecules in NK cells and their capacity to overcome ROS-induced immune suppression. We investigated the effect of H2O2 on resting NK cells, IL-2-activated NK cells and NK cells expanded by coculture with the K562 leukemia cell line genetically modified to express membrane-bound IL-15 and 4-1BB ligand (K562-mb15-41BBL)...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#3
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28210256/transcriptomic-analysis-of-the-innate-antiviral-immune-response-in-porcine-intestinal-epithelial-cells-influence-of-immunobiotic-lactobacilli
#4
Leonardo Albarracin, Hisakazu Kobayashi, Hikaru Iida, Nana Sato, Tomonori Nochi, Hisashi Aso, Susana Salva, Susana Alvarez, Haruki Kitazawa, Julio Villena
Lactobacillus rhamnosus CRL1505 and Lactobacillus plantarum CRL1506 are immunobiotic strains able to increase protection against viral intestinal infections as demonstrated in animal models and humans. To gain insight into the host-immunobiotic interaction, the transcriptomic response of porcine intestinal epithelial (PIE) cells to the challenge with viral molecular associated pattern poly(I:C) and the changes in the transcriptomic profile induced by the immunobiotics strains CRL1505 and CRL1506 were investigated in this work...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28194116/dynamic-and-static-exercises-differentially-affect-plasma-cytokine-content-in-elite-endurance-and-strength-trained-athletes-and-untrained-volunteers
#5
Leonid V Kapilevich, Anna N Zakharova, Anastasia V Kabachkova, Tatyana A Kironenko, Sergei N Orlov
Extensive exercise increases the plasma content of IL-6, IL-8, IL-15, leukemia inhibitory factor (LIF), and several other cytokines via their augmented transcription in skeletal muscle cells. However, the relative impact of aerobic and resistant training interventions on cytokine production remains poorly defined. In this study, we compared effects of dynamic and static load on cytokine plasma content in elite strength- and endurance-trained athletes vs. healthy untrained volunteers. The plasma cytokine content was measured before, immediately after, and 30 min post-exercise using enzyme-linked immunosorbent assay...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28191740/insulin-dependent-cytoplasmic-distribution-of-rab4a-in-mouse-adipocytes-is-inhibited-by-interleukin-6-8-and-15
#6
Maciej Błaszczyk, Małgorzata Gajewska, Mart Milewska, Katarzyna Grzelkowska-Kowalczyk
The purpose of the study was to examine the effect of interleukins, IL-6, IL-8 and IL-15, on insulin-mediated redistribution of Rab4a, an early endosome marker, in mouse 3T3-L1 adipocytes. The interleukins did not affect cell viability; however, cell number was slightly but significantly higher in cultures exposed to IL-8 and IL-15. IL-8 and IL-15 decreased lipid storage in adipocytes, whereas IL-6 had no effect. Rab4A showed cytoplasmic localization, and in control unstimulated adipocytes it was found primarily nearby nucleus, that was supported by cellular fluorescence distribution profile, and by calculated indices, i...
February 13, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28181907/the-role-of-interleukin-15-in-neoplasia
#7
Małgorzata Chłopek, Artur Kowalik, Stanisław Góźdź, Katarzyna Koziak
Interleukin 15 is a pleiotropic cytokine of the four α helix bundle family. Binding to a heterotrimeric receptor complex, which consists of a unique, high affinity IL‑15Rα‑chain and IL-2/IL-15Rβ and IL‑2Rγ chains, IL‑15 activates signaling pathways leading to activation and proliferation of T and B cells, as well as natural killer cells. At the same time, IL‑15 protects effector cells from T regulatory cells and does not induce immune tolerance. The significant regulatory action of IL‑15 on the immune system provides new opportunities for development of anti‑cancer therapies...
January 10, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28164472/the-il15-96522-a-t-functional-polymorphism-is-related-to-the-differentiation-of-th17-cells-and-the-severity-of-hashimoto-s-disease
#8
Y Arakawa, M Watanabe, K Takemura, N Inoue, Y Hidaka, Y Iwatani
To clarify the association between the genetic producibility of IL-15, a pro-inflammatory cytokine, and the pathogenesis of autoimmune thyroid diseases (AITDs), we genotyped +96522 A>T and +82889 A>G polymorphisms in the IL15 gene using 127 patients with Hashimoto's disease (HD), including 55 patients with severe HD and 48 patients with mild HD; 130 patients with Graves' disease (GD), including 52 patients with intractable GD and 44 patients with GD in remission; and 79 healthy volunteers. Both the IL15 +96522 A allele and AA genotype were more frequent in patients with severe HD than in those with mild HD...
February 5, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28161476/markers-of-neuroinflammation-associated-with-alzheimer-s-disease-pathology-in-older-adults
#9
Julius Popp, Aikaterini Oikonomidi, Domilė Tautvydaitė, Loïc Dayon, Michael Bacher, Eugenia Migliavacca, Hugues Henry, Richard Kirkland, India Severin, Jérôme Wojcik, Gene L Bowman
BACKGROUND: In vitro and animal studies have linked neuroinflammation to Alzheimer's disease (AD) pathology. Studies on markers of inflammation in subjects with mild cognitive impairment or AD dementia provided inconsistent results. We hypothesized that distinct blood and cerebrospinal fluid (CSF) inflammatory markers are associated with biomarkers of amyloid and tau pathology in older adults without cognitive impairment or with beginning cognitive decline. OBJECTIVE: To identify blood-based and CSF neuroinflammation marker signatures associated with AD pathology (i...
February 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28154569/regulation-of-nk-cell-activation-and-effector-functions-by-the-il-12-family-of-cytokines-the-case-of-il-27
#10
REVIEW
Norberto Walter Zwirner, Andrea Ziblat
Natural killer (NK) cells are characterized by their ability to detect and induce apoptosis of susceptible target cells and by secretion of immunoregulatory cytokines such as IFN-γ. Activation of these effector functions is triggered upon recognition of tumor and pathogen (mostly virus)-infected cells and because of a bidirectional cross talk that NK cells establish with other cells of myeloid origin such as dendritic cells (DC) and macrophages. A common characteristic of these myeloid cells is their ability to secrete different members of the IL-12 family of cytokines such as IL-12, IL-23, and IL-27 and cytokines such as IL-15 and IL-18...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28145491/altered-expression-of-mir-181a-and-mir-146a-does-not-change-the-expression-of-surface-ncrs-in-human-nk-cells
#11
Mona Rady, Carsten Watzl, Maren Claus, Ola Khorshid, Laila Mahran, Khaled Abou-Aisha
MicroRNAs (miRNAs) play an important role in regulating gene expression and immune responses. Of interest, miR-181a and miR-146a are key players in regulating immune responses and are among the most abundant miRNAs expressed in NK cells. Bioinformatically, we predicted miR-181a to regulate the expression of the natural cytotoxicity receptor NCR2 by seeded interaction with the 3'-untranslated region (3'-UTR). Whereas, miR-146a expression was not significantly different (P = 0.7361), miR-181a expression was, on average 10-fold lower in NK cells from breast cancer patients compared to normal subjects; P < 0...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28142222/flagellar-filament-structural-protein-induces-sj%C3%A3-gren-s-syndrome-like-sialadenitis-in-mice
#12
Tomoaki Higuchi, Ikuko Haruta, Noriyuki Shibata, Naoko Yanagisawa, Junji Yagi
OBJECTIVE: Sjögren's syndrome (SS) is a systemic autoimmune disease that primarily affects lacrimal and salivary glands. We previously reported that FliC derived from E. coli could induce autoimmune pancreatitis-like lesions. From these results, we speculated that FliC could also induce SS-like exocrinopathy. In the present study, we investigated the effects of chronic exposure to FliC on lacrimal and salivary glands and the possibility that it might lead to an autoimmune response. METHODS: C57BL/6 mice were repeatedly injected with FliC and histological changes, serum levels of cytokine/chemokines and autoantibodies were evaluated at different time points after the final injection...
January 31, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28138156/antibody-dependent-cell-cytotoxicity-adcc-immunotherapy-strategies-enhancing-effector-nk-cells
#13
REVIEW
Maria Carmen Ochoa, Luna Minute, Inmaculada Rodriguez, Saray Garasa, Elisabeth Perez-Ruiz, Susana Inogés, Ignacio Melero, Pedro Berraondo
Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). These effectors include not only NK cells but also other CD16(+) subsets such as monocyte/macrophages, NKT cells or γδ T cells. In cancer therapy, ADCC is exploited by antibodies that selectively recognize proteins on the surface of malignant cells. An approach to enhance antitumor activity is to act on effector cells so they are increased in their numbers or enhanced in their individual (on a cell per cell basis) ADCC performance...
January 31, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28130434/selective-progesterone-receptor-modulator-sprm-ulipristal-acetate-upa-and-its-effects-on-the-human-endometrium
#14
L H R Whitaker, A A Murray, R Matthews, G Shaw, A R W Williams, P T K Saunders, H O D Critchley
STUDY QUESTION: What is the impact of administration of the selective progesterone receptor modulator (SPRM), ulipristal acetate (UPA) on the endometrium of women with fibroids? SUMMARY ANSWER: UPA administration altered expression of sex-steroid receptors and progesterone-regulated genes and was associated with low levels of glandular and stromal cell proliferation. WHAT IS KNOWN ALREADY: Administration of all SPRM class members results in PAEC (progesterone receptor modulator associated endometrial changes)...
January 26, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28130082/inflammatory-mediators-associated-with-pressure-ulcer-development-in-individuals-with-pneumonia-following-traumatic-spinal-cord-injury-a-pilot-study
#15
Shilpa Krishnan, Yoram Vodovotz, Patricia E Karg, Gregory Constantine, Gwendolyn A Sowa, Florica J Constantine, David M Brienza
OBJECTIVE: To identify the inflammatory mediators around the time of pneumonia onset associated with concurrent or later onset of pressure ulcers. DESIGN: Retrospective SETTING: Acute hospitalization and inpatient rehabilitation unit of a university medical center. INTERVENTIONS: NA. PARTICIPANTS: Eighty-six individuals with traumatic SCI were included in the initial analyses. Fifteen of the 86 developed pneumonia and had inflammatory mediator data available...
January 24, 2017: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28111009/glomerular-common-gamma-chain-confers-b-and-t-cell-independent-protection-against-glomerulonephritis
#16
Yosu Luque, Dominique Cathelin, Sophie Vandermeersch, Xiaoli Xu, Julie Sohier, Sandrine Placier, Yi-Chun Xu-Dubois, Kevin Louis, Alexandre Hertig, Jean-Christophe Bories, Florence Vasseur, Fabien Campagne, James P Di Santo, Christian Vosshenrich, Eric Rondeau, Laurent Mesnard
Crescentic glomerulonephritis is a life-threatening renal disease that has been extensively studied by the experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) model. Although T cells have a significant role in this model, athymic/nude mice and rats still develop severe renal disease. Here we further explored the contribution of intrinsic renal cells in the development of T-cell-independent GN lesions. Anti-GBM-GN was induced in three strains of immune-deficient mice (Rag2(-/-), Rag2(-/-)Il2rg(-/-), and Rag2(-/-)Il2rb(-/-)) that are devoid of either T/B cells or T/B/NK cells...
January 19, 2017: Kidney International
https://www.readbyqxmd.com/read/28110119/interleukin-15-activates-akt-to-protect-astrocytes-from-oxygen-glucose-deprivation-induced-cell-death
#17
Gilbert Aaron Lee, Yein-Gei Lai, Ray-Jade Chen, Nan-Shih Liao
Astrocytes play a pivotal role in neuronal survival under the condition of post-ischemic brain inflammation, but the relevant astrocyte-derived mediators of ischemic brain injury remain to be defined. IL-15 supports survival of multiple lymphocyte lineages in the peripheral immune system, but the role of IL-15 in inflammatory disease of the central nervous system is not well defined. Recent research has shown an increase of IL-15-expressing astrocytes in the ischemic brain. Since astrocytes promote neuron survival under cerebral ischemia by buffering excess extracellular glutamate and producing growth factors, recovery of astrocyte function could be of benefit for stroke therapy...
January 18, 2017: Cytokine
https://www.readbyqxmd.com/read/28103602/intraocular-cytokines-and-their-correlations-with-clinical-parameters-in-patients-with-myopic-choroidal-neovascularization
#18
Andrey G Shchuko, Natalia V Zaitseva, Tatyana N Yurieva, Elena R Chernykh, Isay M Mikhalevich, Ekaterina Y Shevela, Alina V Grigorieva
PURPOSE: To study cytokine levels in aqueous humor of patients with myopic choroidal neovascularization (mCNV), their correlations with each other and ocular parameters. METHODS: Ophthalmological examination and immunological study of aqueous humor with cytokine levels measurement (Bio-Plex™ Human Cytokine 27-Plex panel; Bio-Rad Laboratories, USA) were performed in 19 patients (19 eyes) with ranibizumab-treated mCNV and compared to 15 patients (15 eyes) with myopia without CNV...
January 20, 2017: Ophthalmologica. Journal International D'ophtalmologie
https://www.readbyqxmd.com/read/28100681/lfa-1-activation-in-nk-cells-and-their-subsets-influence-of-receptors-maturation-and-cytokine-stimulation
#19
Doris Urlaub, Kristine Höfer, Martha-Lena Müller, Carsten Watzl
The integrin LFA-1 is essential for efficient activation and for cytotoxicity of NK cells because it initiates the assembly of the immunological synapse and mediates firm adhesion to the target. LFA-1 is also needed to polarize the cytotoxic machinery of the NK cell toward the target cell. The binding affinity and avidity of integrins can be regulated via inside-out signals from other receptors. In this article, we investigate the signals necessary to activate LFA-1 in human NK cells. Our data show that LFA-1 has a low ligand-binding activity in resting human NK cells, but it can be stimulated by triggering activating receptors, such as 2B4 or CD16, or by coactivation of different receptor combinations...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28099143/desirable-cytolytic-immune-effector-cell-recruitment-by-interleukin-15-dendritic-cells
#20
Heleen H Van Acker, Ottavio Beretta, Sébastien Anguille, Lien De Caluwé, Angela Papagna, Johan M Van den Bergh, Yannick Willemen, Herman Goossens, Zwi N Berneman, Viggo F Van Tendeloo, Evelien L Smits, Maria Foti, Eva Lion
Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells...
January 13, 2017: Oncotarget
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