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https://www.readbyqxmd.com/read/28738233/association-of-the-il-15-and-il-15r%C3%AE-genes-with-celiac-disease
#1
Celia Escudero-Hernández, Leticia Plaza-Izurieta, José A Garrote, José Ramón Bilbao, Eduardo Arranz
Celiac disease is a chronic autoimmune condition triggered by dietary gluten in genetically predisposed individuals and the treatment is a strict gluten-free diet. The major predisposing genes are HLA-DQA1 and HLA-DQB1, but these are not sufficient for disease development. One of the candidate genes worth studying is interleukin (IL)-15 gene, together with its specific receptor, IL-15Rα, as they participate in promoting lymphocyte signaling and survival, and the establishment of appropriate conditions for villous atrophy, then acting as key players in the immunopathogenesis of CD...
July 21, 2017: Cytokine
https://www.readbyqxmd.com/read/28737923/co-silencing-intestinal-transglutaminase-2-and-interleukin-15-using-gelatin-based-nanoparticles-in-an-in-vitro-model-of-celiac-disease
#2
Husain Attarwala, Valerie Clausen, Prasoon Chaturvedi, Mansoor M Amiji
In this study, we have developed type B gelatin-based nanoparticle based siRNA delivery system for silencing of intestinal transglutaminase-2 (TG2) and interleukin-15 (IL-15) genes in cultured human intestinal epithelial cells (Caco-2) and murine alveolar macrophage cells (J774A.1). Small interfering RNA (siRNA) targeting the TG2 or IL-15 gene was encapsulated within gelatin nanoparticles using ethanol-water solvent displacement method. Size, charge and morphology of gelatin nanoparticles were evaluated using Zetasizer instrument and transmission electron microscopy...
July 24, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28734743/adjuvantation-of-inactivated-foot-and-mouth-disease-virus-vaccine-with-il-15-expressing-plasmid-improves-the-immune-response-in-guinea-pigs
#3
Vijay Nagaraj, Lijo John, Singaram Bharatiraja, Hosur Joyappa Dechamma, Golla Ramalinga Reddy
Foot and mouth disease is a highly contagious disease affecting cloven footed animals. Vaccination using inactivated virus is followed to control the disease. As the immune response conferred by the inactivated vaccine is short lived, there is a need for an alternate vaccine with increased duration of immunity. Inclusion of adjuvant which enhances B and T cell responses is one of the strategies to increase the duration of immune responses of the vaccine. Interleukin 15 is one such a cytokine which improves the cell mediated immune response and also involved in the maintenance of memory T and B cells...
July 19, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28729536/weakened-il-15-production-and-impaired-mtor-activation-alter-dendritic-epidermal-t-cell-homeostasis-in-diabetic-mice
#4
Zhongyang Liu, Guangping Liang, Li Gui, Yashu Li, Meixi Liu, Yang Bai, Xiaorong Zhang, Xiaohong Hu, Jian Chen, Chibing Huang, Xusheng Liu, Gaoxing Luo, Jun Wu, Weifeng He
Diabetes is associated with impaired wound healing, which may be caused primarily by a deficiency in dendritic epidermal T cells (DETCs). In the epidermis, IL-15, IGF-1, and mTOR are known to regulate the maintenance of DETCs; however, it is unclear how these molecules may intersect to regulate DETC homeostasis in diabetes. Here, we show that the reduction of DETCs in the epidermis of diabetic mice is caused by altered homeostasis mediated by a reduction in IL-15 levels. Both impaired mTOR activation and reduction of IL-15 in the epidermis play important roles in DETC homeostasis...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28725044/cord-blood-nk-cells-engineered-to-express-il-15-and-a-cd19-targeted-car-show-long-term-persistence-and-potent-anti-tumor-activity
#5
E Liu, Y Tong, G Dotti, H Shaim, B Savoldo, M Mukherjee, J Orange, X Wan, X Lu, A Reynolds, M Gagea, P Banerjee, R Cai, M H Bdaiwi, R Basar, M Muftuoglu, L Li, D Marin, W Wierda, M Keating, R Champlin, E Shpall, K Rezvani
Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T-cells against leukemia and lymphoma with promising clinical results.(1-3) Extending this approach to allogeneic T-cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy...
July 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28713936/epigallocatechin-gallate-attenuates-overload%C3%A2-induced-cardiac-ecm-remodeling-via-restoring-t-cell-homeostasis
#6
Yongsheng Han, Qingtong Wang, Xizhen Fan, Jun Chu, Junfu Peng, Yousheng Zhu, Yan Li, Xiaojing Li, Lei Shen, James Asenso, Shanfeng Li
It has previously been demonstrated that Epigallocatechin gallate (EGCG) has regulatory effects on cellular immunity. The present study explored whether EGCG inhibits the overload‑induced cardiac extracellular matrix (ECM) remodeling through targeting the balance of T cell subpopulations. Sprague‑Dawley rats were subjected to either transverse aortic constriction (TAC) or sham operation. TAC rats were treated with EGCG or valsartan (Val) for 6 weeks. The administration of EGCG or Val ameliorated the overproduction of cardiac collagen, inhibited matrix metalloproteinase (MMP) activity, decreased the expression of tissue inhibitor of MMP‑2, atrial natriuretic peptide and brain natriuretic peptide...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713392/il-15-harnesses-pro-inflammatory-function-of-temra-cd8-in-kidney-transplant-recipients
#7
Gaëlle Tilly, Tra-My Doan-Ngoc, Michelle Yap, Aurélie Caristan, Lola Jacquemont, Richard Danger, Marion Cadoux, Sarah Bruneau, Magali Giral, Pierrick Guerif, Bryan Nicol, Alexandra Garcia, David-Axel Laplaud, Sophie Brouard, Claire Pecqueur Hellman, Nicolas Degauque
The involvement of TEMRA CD8 is evident in a large array of immunological conditions ranging from auto- to allo-immunity. Nevertheless, the factors leading to their accumulation and activation remain ill-defined and, efficient therapeutics to control their inflammatory response is lacking. Here, we show that IL-15-stimulated TEMRA from kidney-transplant (KT) recipients promote inflammation by inducing the expression of CX3CL1 by endothelial cells in an IFN-γ- and TNF-α-dependent manner. The responsiveness of TEMRA to IL-15 is not restricted to chronic stimulation, as TEMRA from healthy volunteers respond earlier and faster when compared to effector memory (EM)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28701509/dendritic-cell-derived-il-32%C3%AE-a-novel-inhibitory-cytokine-of-nk-cell-function
#8
Laurent Gorvel, Daniel Korenfeld, Thomas Tung, Eynav Klechevsky
Cytokines produced by dendritic cells (DCs) can largely determine the direction of immunity. Transcriptional analysis revealed that besides IL-15, IL-32 was the only other cytokine expressed by human Langerhans cells. IL-32 is a human cytokine that exists in four main isoforms. Currently, little is known about the regulation and function of the various IL-32 isoforms. In this study, we found that IL-15 is a potent inducer of IL-32α in DCs. Because IL-15 promotes NK cell activation, we investigated the interplay between IL-32 and IL-15 and their role in NK cell activity...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28689166/ocular-surface-cytokine-profile-in-chronic-stevens-johnson-syndrome-and-its-response-to-mucous-membrane-grafting-for-lid-margin-keratinisation
#9
Srividya Gurumurthy, Geetha Iyer, Bhaskar Srinivasan, Shweta Agarwal, Narayanasamy Angayarkanni
BACKGROUND: To study the tear cytokine and the conjunctival and oral mucosal marker profile in chronic ocular Stevens-Johnson syndrome (SJS) and their alteration following mucous membrane grafting (MMG) for lid margin keratinisation (LMK). METHODS: In a 1-year prospective study, SJS cases (n=25) and age-matched/sex-matched healthy controls (n=25) were recruited. Tear specimen (Schirmer's strip), conjunctival and oral mucosal imprints were collected from controls and SJS cases pre-MMG and post-MMG (at first follow-up, n=17)...
July 8, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28689087/the-histone-deacetylase-inhibitor-saha-simultaneously-reactivates-hiv-1-from-latency-and-up-regulates-nkg2d-ligands-sensitizing-for-natural-killer-cell-cytotoxicity
#10
Maria Giovanna Desimio, Erica Giuliani, Margherita Doria
In pilot HIV-1 eradication studies, patients' immune responses were ineffective at killing viral reservoirs reactivated through latency reversing agents (LRAs) like suberoylanilide hydroxamic acid (SAHA). We hypothesized that T cells harboring reactivated HIV-1 express MIC and ULBP ligands for the activating NKG2D receptor of natural killer (NK) cells. Here, we demonstrated that MICA/B and ULBP2 are induced by SAHA on primary T cells harboring reactivated virus. Using latently HIV-1-infected J-Lat 6.3/8.4/9...
July 6, 2017: Virology
https://www.readbyqxmd.com/read/28674537/increased-il-15-production-and-accumulation-of-highly-differentiated-cd8-effector-memory-t-cells-in-the-bone-marrow-of-persons-with-cytomegalovirus
#11
Luca Pangrazzi, Erin Naismith, Andreas Meryk, Michael Keller, Brigitte Jenewein, Klemens Trieb, Beatrix Grubeck-Loebenstein
Cytomegalovirus (CMV) has been described as a contributor to immunosenescence, thus exacerbating age-related diseases. In persons with latent CMV infection, the CD8(+) T cell compartment is irreversibly changed, leading to the accumulation of highly differentiated virus-specific CD8(+) T cells in the peripheral blood. The bone marrow (BM) has been shown to play a major role in the long-term survival of antigen-experienced T cells. Effector CD8(+) T cells are preferentially maintained by the cytokine IL-15, the expression of which increases in old age...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28671275/curtailed-t-cell-activation-curbs-effector-differentiation-and-generates-cd8-t-cells-with-a-naturally-occuring-memory-stem-cell-phenotype
#12
Veronica Zanon, Karolina Pilipow, Eloise Scamardella, Federica De Paoli, Gabriele De Simone, David A Price, Amaia Martinez Usatorre, Pedro Romero, Domenico Mavilio, Alessandra Roberto, Enrico Lugli
Human T memory stem (TSCM ) cells with superior persistence capacity and effector functions are emerging as important players in the maintenance of long-lived T-cell memory and are thus considered an attractive population to be used in adoptive transfer-based immunotherapy of cancer. However, the molecular signals regulating their generation remain poorly defined. Here we show that curtailed T-cell receptor stimulation curbs human effector CD8(+) T-cell differentiation and allows the generation of CD45RO(-) CD45RA(+) CCR7(+) CD27(+) CD95(+) -phenotype cells from highly purified naïve T-cell precursors, resembling naturally-occurring human TSCM ...
July 3, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28670317/safeguarding-of-fetal-growth-by-mast-cells-and-natural-killer-cells-deficiency-of-one-is-counterbalanced-by-the-other
#13
Nicole Meyer, Katja Woidacki, Marcus Maurer, Ana Claudia Zenclussen
Uterine natural killer cells (uNKs) and mast cells (uMCs) are of crucial importance for spiral artery (SA) remodeling and placentation. Mice deficient for both NKs and MCs including uNKs and uMCs show markedly impaired SA remodeling and their fetuses are growth-retarded. In contrast, the absence of either NKs or MCs results in only minor impairment. This suggests that uNKs can compensate for the effects of uMCs on SA remodeling and vice versa. To test this hypothesis, we assessed uNK numbers in uMC-deficient mice as well as uMC numbers in uNK-depleted mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28659917/a-two-phase-expansion-protocol-combining-interleukin-il-15-and-il-21-improves-natural-killer-cell-proliferation-and-cytotoxicity-against-rhabdomyosarcoma
#14
Juliane Wagner, Viktoria Pfannenstiel, Anja Waldmann, Judith W J Bergs, Boris Brill, Sabine Huenecke, Thomas Klingebiel, Franz Rödel, Christian J Buchholz, Winfried S Wels, Peter Bader, Evelyn Ullrich
Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children. Despite intensive research in recent decades the prognosis for patients with metastatic or relapsed diseases has hardly improved. New therapeutic concepts in anti-tumor therapy aim to modulate the patient's immune system to increase its aggressiveness or targeted effects toward tumor cells. Besides surgery, radiotherapy and chemotherapy, immune activation by direct application of cytokines, antibodies or adoptive cell therapy are promising approaches...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28657314/discovery-of-a-small-molecule-inhibitor-of-interleukin-15-pharmacophore-based-virtual-screening-and-hit-optimization
#15
Agnès Quéméner, Mike Maillasson, Laurence Arzel, Benoit Sicard, Romy Vomiandry, Erwan Mortier, Didier Dubreuil, Yannick Jacques, Jacques Lebreton, Monique Mathé-Allainmat
Interleukin (IL)-15 is a pleiotropic cytokine, which is structurally close to IL-2 and shares with it the IL-2 β and γ receptor (R) subunits. By promoting the activation and proliferation of NK, NK-T, and CD8+ T cells, IL-15 plays important roles in innate and adaptative immunity. Moreover, the association of high levels of IL-15 expression with inflammatory and autoimmune diseases has led to the development of various antagonistic approaches targeting IL-15. This study is an original approach aimed at discovering small-molecule inhibitors impeding IL-15/IL-15R interaction...
July 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28650254/proteomics-to-predict-the-response-to-tumour-necrosis-factor-%C3%AE-inhibitors-in-rheumatoid-arthritis-using-a-supervised-cluster-analysis-based-protein-score
#16
Bvj Cuppen, Rde Fritsch-Stork, I Eekhout, W de Jager, A C Marijnissen, Jwj Bijlsma, M Custers, J M van Laar, Fpjg Lafeber, Pmj Welsing
OBJECTIVE: In rheumatoid arthritis (RA), it is of major importance to identify non-responders to tumour necrosis factor-α inhibitors (TNFi) before starting treatment, to prevent a delay in effective treatment. We developed a protein score for the response to TNFi treatment in RA and investigated its predictive value. METHOD: In RA patients eligible for biological treatment included in the BiOCURA registry, 53 inflammatory proteins were measured using xMAP® technology...
June 26, 2017: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/28644973/il-18-il-15-il-12-synergy-induces-elevated-and-prolonged-ifn-%C3%AE-production-by-ex-vivo-expanded-nk-cells-which-is-not-due-to-enhanced-stat4-activation
#17
Evan Lusty, Sophie M Poznanski, Karen Kwofie, Talveer S Mandur, Dean A Lee, Carl D Richards, Ali A Ashkar
The synergistic effect of IL-18/IL-15/IL-12 stimulation potently activates NK cells, inducing high levels of IFN-γ production. As a result of this potent stimulatory effect, NK cell pre-activation with IL-18/IL-15/IL-12 is being developed as a cancer immunotherapy. Ex vivo expansion of NK cells enables the efficient generation of large numbers of NK cells for wide-scale and repeated therapeutic use, and is thus an important source of NK cells for clinical application. However, the effects of IL-18/IL-15/IL-12 stimulation on ex vivo expanded NK cells have not yet been assessed...
June 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28639033/functional-restoration-of-cd56-bright-nk-cells-facilitates-immune-control-via-il-15-and-nkg2d-in-patients-under-antiviral-treatment-for-chronic-hepatitis-b
#18
Tao Chen, Lin Zhu, Aichao Shi, Lin Ding, Xiaoping Zhang, Zhenmin Tan, Wei Guo, Weiming Yan, Meifang Han, Jidong Jia, Xiaoping Luo, Detlef Schuppan, Qin Ning
BACKGROUND AND AIMS: Hepatitis B virus (HBV) is intrinsically immunogenic, with long-lasting immune control in many patients. However, the mechanisms and key cell types underlying effective immune control are incompletely understood. METHODS: We studied the restoration of natural killer (NK) cell numbers and function post antiviral treatment in 52 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who received telbivudine (LdT) for 48 weeks...
June 20, 2017: Hepatology International
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#19
Johan Mj Van den Bergh, Evelien Ljm Smits, Zwi N Berneman, Tim Ja Hutten, Hans De Reu, Viggo Fi Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DCs) is an appealing strategy to boost the GVT-response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28636955/inflammatory-ly6c-high-monocytes-protect-against-candidiasis-through-il-15-driven-nk-cell-neutrophil-activation
#20
Jorge Domínguez-Andrés, Lidia Feo-Lucas, María Minguito de la Escalera, Leticia González, María López-Bravo, Carlos Ardavín
Neutrophils play a crucial role in defense against systemic candidiasis, a disease associated with a high mortality rate in patients receiving immunosuppressive therapy, although the early immune mechanisms that boost the candidacidal activity of neutrophils remain to be defined in depth. Here, we used a murine model of systemic candidiasis to explore the role of inflammatory Ly6C(high) monocytes in NK cell-mediated neutrophil activation during the innate immune response against C. albicans. We found that efficient anti-Candida immunity required a collaborative response between the spleen and kidney, which relied on type I interferon-dependent IL-15 production by spleen inflammatory Ly6C(high) monocytes to drive efficient activation and GM-CSF release by spleen NK cells; this in turn was necessary to boost the Candida killing potential of kidney neutrophils...
June 20, 2017: Immunity
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