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https://www.readbyqxmd.com/read/28861771/recombinant-rabies-virus-expressing-il-15-enhances-immunogenicity-through-promoting-the-activation-of-dendritic-cells-in-mice
#1
Tiange Chen, Yajing Zhang, Zhao Wang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Zhen F Fu, Ling Zhao, Ming Zhou
Rabies remains a public health threat that kills approximately 59,000 people worldwide each year, most of which are from the developing countries of Africa and Asia where dog rabies are endemic. Therefore, developing an affordable and efficacious vaccine is crucial for rabies control in these countries. Interleukin (IL)-15, an immunoregulatory cytokine, is a pluripotent molecule with therapeutic potential, which targets many cell types and links the innate and adaptive immune system. In this study, IL-15 gene was cloned and inserted into the genome of a recombinant rabies virus (RABV) strain LBNSE (designated as LBNSE-IL15), and the effect of over-expression of IL-15 on the immunogenicity of RABV was investigated...
August 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28842470/il15-infusion-of-cancer-patients-expands-the-subpopulation-of-cytotoxic-cd56bright-nk-cells-and-increases-nk-cell-cytokine-release-capabilities
#2
Sigrid Dubois, Kevin C Conlon, Jurgen R Müller, Jennifer Hsu-Albert, Nancy Beltran, Bonita R Bryant, Thomas A Waldmann
The cytokine IL15 is required for survival and activation of NK cells as well as expansion of NK-cell populations. Here we compare the effects of continuous IL15 infusions on NK-cell subpopulations in cancer patients. Infusions affected the CD56bright NK-cell subpopulation in that the expansion rates exceeded those of CD56dim NK-cell populations with a 350-fold increase in their total cell numbers compared to 20-fold expansion for the CD56 dim subset. CD56bright NK cells responded with increased cytokine release to various stimuli, as expected given their immunoregulatory functions...
August 25, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28827115/effect-of-il15-rs10833-and-scarb1-rs10846744-on-virologic-responses-in-chronic-hepatitis-c-patients-treated-with-pegylated-interferon-%C3%AE-and-ribavirin
#3
Sahar Sadeghi, Mehdi Davari, Esmaeil Asli, Safoora Gharibzadeh, Farzam Vaziri, Fatemeh Rahimi Jamnani, Abolfazl Fateh, Seyed Davar Siadat
The scavenger receptor type B class I (SCARBI) is known to be involved in the entry of hepatitis C virus (HCV) into the host, while interleukin-15 (IL15) is an important cytokine in both the innate and acquired immune responses against HCV infection. We investigated the association of IL15 rs10833 or SCARB1 rs10846744 polymorphisms with treatment responses in patients with chronic HCV (CHC). SCARB1 rs10846744 and IL15 rs10833 were identified in 365 treatment-naïve CHC patients through genotyping by TaqMan® Real-Time PCR and PCR-restriction fragment length polymorphism (RFLP), respectively...
August 4, 2017: Gene
https://www.readbyqxmd.com/read/28811289/primary-tumors-limit-metastasis-formation-through-induction-of-il15-mediated-crosstalk-between-patrolling-monocytes-and-nk-cells
#4
Hiroshi Kubo, Sofia Mensurado, Natacha Goncalves-Sousa, Karine Serre, Bruno Silva-Santos
Metastases are responsible for the vast majority of cancer-related deaths. Although tumor cells can become invasive early during cancer progression, metastases formation typically occurs as a late event. How the immune response to primary tumors may dictate this outcome remains poorly understood, which hampers our capacity to manipulate it therapeutically. Here we used a two-step experimental model, based on the highly aggressive B16F10 melanoma, that temporally segregates the establishment of primary tumors (subcutaneously) and the formation of lung metastases (from intravenous injection)...
August 15, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28807496/cd4-effector-t-cell-differentiation-is-controlled-by-il-15-that-is-expressed-and-presented-in-trans
#5
Adam T Waickman, Davinna L Ligons, SuJin Hwang, Joo-Young Park, Vanja Lazarevic, Noriko Sato, Changwan Hong, Jung-Hyun Park
T cells are both producers and consumers of cytokines, and autocrine cytokine signaling plays a critical role in T cell immunity. IL-15 is a homeostatic cytokine for T cells that also controls inflammatory immune responses. An autocrine role of T cell-derived IL-15, however, remains unclear. Here we examined IL-15 expression and signaling upon effector T cell differentiation in mice, and, surprisingly, found that CD4 T cells did not express IL-15. CD4 T cells lacked Il15 gene reporter activity, did not contain IL-15 transcripts, and did not produce IL-15Rα, the proprietary IL-15 receptor required for IL-15 trans-presentation...
August 11, 2017: Cytokine
https://www.readbyqxmd.com/read/28738233/association-of-the-il-15-and-il-15r%C3%AE-genes-with-celiac-disease
#6
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/28670317/safeguarding-of-fetal-growth-by-mast-cells-and-natural-killer-cells-deficiency-of-one-is-counterbalanced-by-the-other
#7
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/28651743/the-combination-of-nk-and-cd8-t-cells-with-ccl20-il15-armed-oncolytic-adenoviruses-enhances-the-growth-suppression-of-tert-positive-tumor-cells
#8
Jun-Feng Ye, Wen-Xi Qi, Ming-Yuan Liu, Yang Li
Adoptive immunotherapy and targeted gene therapy have been extensively used to eliminate tumor cells. The combination treatment is capable of efficiently generating an effective antitumor immune response and disrupting tumor-induced tolerance. Moreover, effective antitumor immune responses are dependent on coordinate interaction among various effector cells. This study focused on whether the combination of cytotoxic effector cell-based adoptive immunotherapy and CCL20/IL15-armed oncolytic adenoviruses could induce enhanced antitumor activity...
August 2017: Cellular Immunology
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
#9
Johan M J Van den Bergh, Evelien L J M Smits, Zwi N Berneman, Tim J A Hutten, Hans De Reu, Viggo F I 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 (DC) 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)...
August 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28602725/il15ra-is-required-for-osteoblast-function-and-bone-mineralization
#10
Emanuele Loro, Girish Ramaswamy, Abhishek Chandra, Wei-Ju Tseng, Manoj K Mishra, Eileen M Shore, Tejvir S Khurana
Interleukin-15 receptor alpha (IL15RA) is an important component of interleukin-15 (IL15) pro-inflammatory signaling. In addition, IL15 and IL15RA are present in the circulation and are detected in a variety of tissues where they influence physiological functions such as muscle contractility and overall metabolism. In the skeletal system, IL15RA was previously shown to be important for osteoclastogenesis. Little is known, however, about its role in osteoblast function and bone mineralization. In this study, we evaluated bone structural and mechanical properties of an Il15ra whole-body knockout mouse (Il15ra(-/-)) and used in vitro and bioinformatic analyses to understand the role IL15/IL15RA signaling on osteoblast function...
October 2017: Bone
https://www.readbyqxmd.com/read/28550091/transgenic-expression-of-il15-improves-antiglioma-activity-of-il13ralpha2-car-t-cells-but-results-in-antigen-loss-variants
#11
Giedre Krenciute, Brooke L Prinzing, Zhongzhen Yi, Meng-Fen Wu, Hao Liu, Gianpietro Dotti, Irina V Balyasnikova, Stephen Gottschalk
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is virtually incurable with conventional therapies. Immunotherapy with T cells expressing GBM-specific chimeric antigen receptors (CARs) is an attractive approach to improve outcomes. Although CAR T cells targeting GBM antigens such as IL13Ralpha2 (interleukin 13 Receptor Subunit Alpha 2), HER2 (human epidermal growth factor receptor 2), and EGFRvIII (epidermal growth factor receptor variant III) have had antitumor activity in preclinical models, early phase clinical testing has demonstrated limited antiglioma activity...
May 26, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28507940/cord-blood-cells-responses-to-il2-il7-and-il15-cytokines-for-mtor-expression
#12
Anahita Mohammadian, Elahe Naderali, Seyedeh Momeneh Mohammadi, Aliakbar Movasaghpour, Behnaz Valipour, Mohammad Nouri, Hojjatollah Nozad Charoudeh
Purpose: Mammalian target of rapamycin (mTOR)is important in hematopoiesis and affect cell growth,differentiation and survival. Although previous studies were identified the effect of cytokines on the mononuclear cells development however the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim of this study was to evaluate mTOR expression in cord blood mononuclear and cord blood stem cells (CD34(+) cells) in culture conditions for lymphoid cell development. Methods: Isolation of The mononuclear cells (MNCs) from umbilical cord blood were done with use of Ficollpaque density gradient...
April 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28507797/il15-induces-a-potent-antitumor-activity-in-nk-cells-isolated-from-malignant-pleural-effusions-and-overcomes-the-inhibitory-effect-of-pleural-fluid
#13
D Croxatto, S Martini, L Chiossone, F Scordamaglia, C F Simonassi, L Moretta, M C Mingari, P Vacca
Natural Killer (NK) cells are capable of recognizing and killing cancer cells and play an important role in tumor immunosurveillance. However, tumor-infiltrating NK cells are frequently impaired in their functional capability. A remarkable exception is represented by NK cells isolated from malignant pleural effusions (PE) that are not anergic and, upon IL2-induced activation, efficiently kill tumor cells. Although IL2 is used in various clinical trials, severe side effects may occur in treated patients. In this study, we investigated whether also other clinical-grade cytokines could induce strong cytotoxicity in NK cells isolated from pleural fluid of patients with primary or metastatic tumors of different origins...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28449719/interference-of-retroviral-envelope-with-vaccine-induced-cd8-t-cell-responses-is-relieved-by-co-administration-of-cytokine-encoding-vectors
#14
Nadine Bongard, Dennis Lapuente, Sonja Windmann, Ulf Dittmer, Matthias Tenbusch, Wibke Bayer
BACKGROUND: Retroviral envelope (Env) proteins are known to exhibit immunosuppressive properties, which become apparent not only in retroviral infections, but also in gene-based immunizations using retroviral immunogens, where envelope interferes with the induction of CD8(+) T cell responses towards another, simultaneously or subsequently delivered, immunogen. RESULTS: In the Friend retrovirus mouse model, immunization with a plasmid encoding the Friend murine leukemia virus (F-MuLV) Leader-Gag protein resulted in induction of a strong GagL85-93-specific CD8(+) T cell response, while the response was completely abrogated by co-immunization with an F-MuLV Env-encoding plasmid...
April 27, 2017: Retrovirology
https://www.readbyqxmd.com/read/28432524/correlation-of-serum-mmp3-and-other-biomarkers-with-clinical-outcomes-in-patients-with-ankylosing-spondylitis-a-pilot-study
#15
Dongyi He, Qi Zhu, Quan Zhou, Qing Qi, Hongmei Sun, Liza M Zachariah, Grace Wang, John D Reveille, Yongtao Guan, Xiaodong Zhou
The studies aimed to assess a set of biomarkers for their correlations with disease activity/severity of patients with ankylosing spondylitis (AS). A total of 24 AS patients were treated with etanercept and prospectively followed for 12 weeks. Serum levels of TNF-α, IFN-γ, TGF-β, IL6, IL15, IL17, MMP3, and MICA were measured at baseline and after treatment. The change of these biomarkers was analyzed for correlations with MRI indices for joint inflammation, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, AS Disease Activity Score, serum CRP, and ESR...
August 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28424693/human-melanoma-derived-extracellular-vesicles-regulate-dendritic-cell-maturation
#16
Rachel L G Maus, James W Jakub, Wendy K Nevala, Trace A Christensen, Klara Noble-Orcutt, Zohar Sachs, Tina J Hieken, Svetomir N Markovic
Evolution of melanoma from a primary tumor to widespread metastasis is crucially dependent on lymphatic spread. The mechanisms regulating the initial step in metastatic dissemination via regional lymph nodes remain largely unknown; however, evidence supporting the establishment of a pre-metastatic niche is evolving. We have previously described a dysfunctional immune profile including reduced expression of dendritic cell (DC) maturation markers in the first node draining from the primary tumor, the sentinel lymph node (SLN)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28395334/natural-killer-cell-deficiency-alters-placental-development-in-rats
#17
Stephen J Renaud, Regan L Scott, Damayanti Chakraborty, Mohammad A K Rumi, Michael J Soares
Natural killer (NK) cells are the most prevalent leukocyte population in the uterus during early pregnancy. Natural killer cells contribute to uterine vascular (spiral artery) remodeling in preparation for the increased demand on these vessels later in pregnancy. A second wave of spiral artery modification is directed by invasive trophoblast cells. The significance of the initial wave of NK-cell-mediated vascular remodeling in species exhibiting deep trophoblast invasion such as humans and rats is not known...
January 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28185567/from-comorbidities-of-chronic-obstructive-pulmonary-disease-to-identification-of-shared-molecular-mechanisms-by-data-integration
#18
David Gomez-Cabrero, Jörg Menche, Claudia Vargas, Isaac Cano, Dieter Maier, Albert-László Barabási, Jesper Tegnér, Josep Roca
BACKGROUND: Deep mining of healthcare data has provided maps of comorbidity relationships between diseases. In parallel, integrative multi-omics investigations have generated high-resolution molecular maps of putative relevance for understanding disease initiation and progression. Yet, it is unclear how to advance an observation of comorbidity relations (one disease to others) to a molecular understanding of the driver processes and associated biomarkers. RESULTS: Since Chronic Obstructive Pulmonary disease (COPD) has emerged as a central hub in temporal comorbidity networks, we developed a systematic integrative data-driven framework to identify shared disease-associated genes and pathways, as a proxy for the underlying generative mechanisms inducing comorbidity...
November 22, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28182609/genetic-polymorphisms-associated-with-liver-disease-progression-in-hiv-hcv-coinfected-patients
#19
REVIEW
Luz M Medrano, María A Jiménez-Sousa, Amanda Fernández-Rodríguez, Salvador Resino
The pathogenic mechanisms of the accelerated progression of liver injury in HIV/HCV coinfection are incompletely understood. The progression of liver disease is variable between individuals having similar risk factors, suggesting that genetic background is an important contributor. The aim of this review is to give a summary of all single nucleotide polymorphisms associated with the severity of liver disease in patients coinfected with HIV and HCV reported in the literature. Therefore, a systematic search for articles published was made, 17 of which were selected for this review...
January 2017: AIDS Reviews
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
#20
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...
April 2017: International Journal of Immunogenetics
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