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https://www.readbyqxmd.com/read/28634034/absence-of-%C3%AE-chain-in-keratinocytes-alters-chemokine-secretion-resulting-in-reduced-immune-cell-recruitment
#1
Karolin Nowak, Daniela Linzner, Adrian J Thrasher, Paul F Lambert, Wei Li Di, Siobhan O Burns
Loss of function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency (SCID) characterised by lack of T and natural killer cells and infant death from infection. Haematopoietic stem cell transplantation or gene therapy offer cure but despite successful replacement of lymphoid immune lineages a long-term risk of severe cutaneous human papilloma virus (HPV) infections persists, possibly related to persistent γc-deficiency in other cell types. Here we demonstrate that keratinocytes, the only cell type directly infected by HPV, express functional γc and its co-receptors...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28633645/generation-of-populations-of-antigen-specific-cytotoxic-t-cells-using-dcs-transfected-with-dna-construct-encoding-her2-neu-tumor-antigen-epitopes
#2
Maria Kuznetsova, Julia Lopatnikova, Julia Khantakova, Rinat Maksyutov, Amir Maksyutov, Sergey Sennikov
BACKGROUND: Recent fundamental and clinical studies have confirmed the effectiveness of utilizing the potential of the immune system to remove tumor cells disseminated in a patient's body. Cytotoxic T lymphocytes (CTLs) are considered the main effectors in cell-mediated antitumor immunity. Approaches based on antigen presentation to CTLs by dendritic cells (DCs) are currently being intensively studied, because DCs are more efficient in tumor antigen presentation to T cells through their initiation of strong specific antitumor immune responses than other types of antigen-presenting cells...
June 20, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28628613/immunosuppressive-and-angiogenic-cytokine-profile-associated-with-bartonella-bacilliformis-infection-in-post-outbreak-and-endemic-areas-of-carrion-s-disease-in-peru
#3
Maria J Pons, Cláudia Gomes, Ruth Aguilar, Diana Barrios, Miguel Angel Aguilar-Luis, Joaquim Ruiz, Carlota Dobaño, Juana Del Valle-Mendoza, Gemma Moncunill
Analysis of immune responses in Bartonella bacilliformis carriers are needed to understand acquisition of immunity to Carrion's disease and may allow identifying biomarkers associated with bacterial infection and disease phases. Serum samples from 144 healthy subjects from 5 villages in the North of Peru collected in 2014 were analyzed. Four villages had a Carrion's disease outbreak in 2013, and the other is a traditionally endemic area. Thirty cytokines, chemokines and growth factors were determined in sera by fluorescent bead-based quantitative suspension array technology, and analyzed in relation to available data on bacteremia quantified by RT-PCR, and IgM and IgG levels measured by ELISA against B...
June 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28628013/modulation-of-antitumor-immune-response-in-mouse-prostate-cancer-model
#4
N Mitskevich, T Tsertsvadze, K Mchedlishvili, K Matchavariani, G Guruli
Aim of study - prostate cancer is second most common cancer in men worldwide, and fifth leading cause of death from cancer in men (6.6% of the total men deaths). Unfortunately, once cancer spreads outside of prostate, it becomes incurable. Androgen deprivation can provide some relief, but resistance will develop eventually, and at that time no effective treatment options are left to the patient. Therefore, the search of alternative treatment modalities is paramount. In this article we evaluated the role of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator - Lenalidomide and their possible impact on the immune response in the murine prostate cancer model...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28620098/cytokine-signaling-in-the-development-and-homeostasis-of-regulatory-t-cells
#5
Kevin H Toomer, Thomas R Malek
Cytokine signaling is indispensable for regulatory T-cell (Treg) development in the thymus, and also influences the homeostasis, phenotypic diversity, and function of Tregs in the periphery. Because Tregs are required for establishment and maintenance of immunological self-tolerance, investigating the role of cytokines in Treg biology carries therapeutic potential in the context of autoimmune disease. This review discusses the potent and diverse influences of interleukin (IL)-2 signaling on the Treg compartment, an area of knowledge that has led to the use of low-dose IL-2 as a therapy to reregulate autoaggressive immune responses...
June 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#6
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28606589/regulatory-effects-of-interleukin-il-15-on-allergen-induced-airway-obstruction
#7
Sathisha Upparahalli Venkateshaiah, Xiang Zhu, Priya Rajavelu, Rituraj Niranjan, Murli Manohar, Alok K Verma, Joseph A Lasky, Anil Mishra
BACKGROUND: Airway obstruction is a physiologic feature of asthma and IL-15 may have an important role in the pathogenesis of asthma. OBJECTIVE: We tested the hypothesis that regulation of IL-15 is critical for the preservation of allergen-induced airway hyperresponsiveness (AHR), airway resistance and compliance in response to methacholine. METHODS: Airway inflammation, AHR, resistance and compliance were assessed in IL-15- gene deficient mice and IL-15 overexpressing mice in an allergen-induced murine model of asthma...
June 9, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28602493/alcohol-attenuates-myocardial-ischemic-injury
#8
Laura A Scrimgeour, Brittany A Potz, Nassrene Y Elmadhun, Louis M Chu, Frank W Sellke
BACKGROUND: Moderate alcohol consumption is cardioprotective but the mechanism of action remains unclear. Nuclear factor κ-B regulates the expression of genes involved in inflammation, stress, and apoptosis. We used a swine model of diet-induced metabolic syndrome to investigate the effects of red wine and vodka on nuclear factor κ-B signaling and cytokine activity in chronically ischemic myocardium. METHODS: Yorkshire swine were given a high-fat diet for 4 weeks; an ameroid constrictor was then placed on the left circumflex artery...
June 8, 2017: Surgery
https://www.readbyqxmd.com/read/28602436/car-t-cells-administered-in-combination-with-lymphodepletion-and-pd-1-inhibition-to-patients-with-neuroblastoma
#9
Andras Heczey, Chrystal U Louis, Barbara Savoldo, Olga Dakhova, April Durett, Bambi Grilley, Hao Liu, Mengfeng F Wu, Zhuyong Mei, Adrian Gee, Birju Mehta, Huimin Zhang, Nadia Mahmood, Haruko Tashiro, Helen E Heslop, Gianpietro Dotti, Cliona M Rooney, Malcolm K Brenner
Targeting disialoganglioside (GD2) on neuroblastoma (NB) with T cells expressing a first-generation chimeric antigen receptor (CAR) was safe, but the cells had poor expansion and long-term persistence. We developed a third-generation GD2-CAR (GD2-CAR3) and hypothesized that GD2-CAR3 T cells (CARTs) would be safe and effective. This phase 1 study enrolled relapsed or refractory NB patients in three cohorts. Cohort 1 received CART alone, cohort 2 received CARTs plus cyclophosphamide and fludarabine (Cy/Flu), and cohort 3 was treated with CARTs, Cy/Flu, and a programmed death-1 (PD-1) inhibitor...
June 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28592627/cytokines-are-markers-of-the-clostridium-difficile-induced-inflammatory-response-and-predict-disease-severity
#10
Hua Yu, Kevin Chen, Ying Sun, Mihaela Carter, Kevin W Garey, Tor C Savidge, Sridevi Devaraj, Mary Elizabeth Tessier, Erik C von Rosenvinge, Ciaran P Kelly, Marcela F Pasetti, Hanping Feng
The host immune response affects pathogen virulence in Clostridium difficile infection (CDI). Thus, cytokine responses to CDI are likely associated with disease initiation and progression. Understanding the molecular drivers of inflammation and biochemical markers of disease severity are important for developing novel therapies and predicting the disease prognosis. In this study, we investigated cytokine production in patients with CDI and evaluated the potential of cytokines to serve as biomarkers for CDI and predictors of disease severity...
June 7, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28588637/effect-of-acupuncture-on-endometrial-angiogenesis-and-uterus-dendritic-cells-in-coh-rats-during-peri-implantation-period
#11
Haoxu Dong, Zhiyan Zhong, Wei Chen, Xiao Wu, Qing Zhang, Guangying Huang, Wei Yang
This study was to explore the mechanism of acupuncture on regulating the endometrial angiogenesis and uterus dendritic cells (uDCs) during the peri-implantation period. Rats, in early pregnancy, were randomized into five groups: normal (N), model (M), acupuncture (A), progesterone (P), and A + P groups. The COH model was established using pregnant mare serum, combined with human chorionic gonadotrophin. Endometrium was collected on days 4, 6, and 8 (D4, D6, and D8) of gestation. Compared with group M, both VEGF and FGF-2 protein and mRNA levels were significantly lower on D4 and higher on D6 and D8 (P < 0...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28582647/inflammatory-serum-cytokines-and-chemokines-increase-associated-with-the-disease-extent-in-pediatric-langerhans-cell-histiocytosis
#12
Akira Morimoto, Yukiko Oh, Sachie Nakamura, Yoko Shioda, Tomomi Hayase, Toshihiko Imamura, Kazuko Kudo, Shinsaku Imashuku
OBJECTIVE: Langerhans cell histiocytosis (LCH) is characterized by immature dendritic cell proliferation, infiltration of LCH lesions by various inflammatory cells, and a lesional cytokine storm. It is classified into three groups on the basis of disease extent, namely, multisystem with risk-organ involvement (MS+), multisystem without risk-organ involvement (MS-), and single-system (SS) disease. We comprehensively analyzed whether serum levels of cytokines/chemokines reflect the disease extent...
June 2, 2017: Cytokine
https://www.readbyqxmd.com/read/28581883/discovery-and-characterization-of-a-novel-humanized-anti-il-15-antibody-and-its-relevance-for-the-treatment-of-refractory-celiac-disease-and-eosinophilic-esophagitis
#13
Alain P Vicari, Alain M Schoepfer, Bertrand Meresse, Laurence Goffin, Olivier Léger, Soheila Josserand, Nicolas Guégan, Shida Yousefi, Alex Straumann, Nadine Cerf-Bensussan, Hans-Uwe Simon, Yolande Chvatchko
Interleukin-15 (IL-15) is a critical regulator of immune responses, especially at mucosal interfaces within the gastro-intestinal tract. Here, we describe the discovery and characterization of a humanized antibody to IL-15. Data from its epitope and mode of action, cell biology and primate pharmacology, as well as translational studies in human samples and in vivo proof-of-concept experiments in mouse models demonstrate the therapeutic potential of this new antibody targeting IL-15 for refractory celiac disease and eosinophilic esophagitis...
June 5, 2017: MAbs
https://www.readbyqxmd.com/read/28577104/level-of-interleukins-il-6-and-il-15-in-blood-plasma-of-mice-after-forced-swimming-test
#14
L V Kapilevich, T A Kironenko, A N Zakharova, A V Kabachkova, S N Orlov
We measured the concentrations of IL-6 and IL-15 in blood plasma of mice at different terms after forced swimming, taking into account exercise intensity and preliminary training. It was shown that training was an important factor affecting blood plasma level of IL both at rest and after single forced swimming: in trained animals, the concentration of both myokines increased immediately after swimming, while in untrained animals, this increase was observed only after 5 h. Changes in cytokine production against the background of training can be associated with various factors, including neuroendocrine mechanisms, stress, modification of intracellular signaling, as well as reorganization of transcriptional mechanisms in muscle fibers...
June 3, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28576209/vegf-a-is-increased-in-exogenous-endophthalmitis
#15
Mark E Seamone, Darrell R Lewis, Ian D Haidl, R Rishi Gupta, Daniel M O' Brien, John Dickinson, Arif Samad, Jean S Marshall, Alan F Cruess
OBJECTIVE: Exogenous endophthalmitis is an ophthalmologic emergency defined by panocular inflammation. Vascular endothelial growth factor A (VEGF-A) contributes to inflammation by promoting chemotaxis of monocytes and granulocytes and by increasing vascular permeability. The purpose of this article is to determine if VEGF-A is elevated in the vitreous samples obtained from individuals with exogenous endophthalmitis. METHODS: Vitreous samples from individuals with exogenous endophthalmitis (n = 18) were analyzed via Luminex assay and enzyme-linked immunosorbent assay for the cytokines VEGF-A, tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8 (chemokine [CXCL]-8), IL-1β, IL-10, IL-12p70, IL-33, interferon (IFN)-γ, IFN-α, IFN-β, chemokine ligand (CCL)-3, IL-2, IL-5, IL-15, CXCL-10, CCL-2, IL-1Ra, CCL-5, IL-17, and CCL-11...
June 2017: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
https://www.readbyqxmd.com/read/28574833/new-interleukin-15-superagonist-il-15sa-significantly-enhances-graft-versus-tumor-activity
#16
Cavan P Bailey, Tulin Budak-Alpdogan, Christopher T Sauter, Michelle M Panis, Cihangir Buyukgoz, Emily K Jeng, Hing C Wong, Neal Flomenberg, Onder Alpdogan
Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28555134/the-transcription-factor-znf683-hobit-regulates-human-nk-cell-development
#17
Mirte Post, Angelica Cuapio, Markus Osl, Dorit Lehmann, Ulrike Resch, David M Davies, Martin Bilban, Bernhard Schlechta, Wolfgang Eppel, Amit Nathwani, Dagmar Stoiber, Jan Spanholtz, Emilio Casanova, Erhard Hofer
We identified ZNF683/HOBIT as the most highly upregulated transcription factor gene during ex vivo differentiation of human CD34(+) cord blood progenitor cells to CD56(+) natural killer (NK) cells. ZNF683/HOBIT mRNA was preferentially expressed in NK cells compared to other human peripheral blood lymphocytes and monocytes. During ex vivo differentiation, ZNF683/HOBIT mRNA started to increase shortly after addition of IL-15 and further accumulated in parallel to the generation of CD56(+) NK cells. shRNA-mediated knockdown of ZNF683/HOBIT resulted in a substantial reduction of CD56(-)CD14(-) NK-cell progenitors and the following generation of CD56(+) NK cells was largely abrogated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28550199/comprehensive-approach-for-identifying-the-t-cell-subset-origin-of-cd3-and-cd28-antibody-activated-chimeric-antigen-receptor-modified-t-cells
#18
Michael Schmueck-Henneresse, Bilal Omer, Thomas Shum, Haruko Tashiro, Maksim Mamonkin, Natalia Lapteva, Sandhya Sharma, Lisa Rollins, Gianpietro Dotti, Petra Reinke, Hans-Dieter Volk, Cliona M Rooney
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO(+)CCR7(-) effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28546929/aqueous-proinflammatory-cytokines-in-acute-primary-angle-closure-eyes
#19
Yao-Ming Liu, Shi-Da Chen, Xing-Yi Li, Wen-Bin Huang, Fei Li, Jia-Wei Wang, Ying-Qi Li, Xiu-Lan Zhang
AIM: To evaluate changes of proinflammatory cytokines in aqueous humor of patients with acute primary angle-closure (APAC) and age-related cataracts. METHODS: Twenty eyes of 20 APAC patients and 15 eyes of 15 age-related cataract patients were included in this cross-sectional study. Aqueous humor samples were collected prospectively. The levels of 20 proinflammatory cytokines were evaluated in the aqueous humor of the APAC and cataract patients using the multiplex bead immunoassay technique...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28546021/sodium-butyrate-improved-intestinal-immune-function-associated-with-nf-%C3%AE%C2%BAb-and-p38mapk-signalling-pathways-in-young-grass-carp-ctenopharyngodon-idella
#20
Li Tian, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Fei Xie, Lin Feng
The present study evaluated the effect of dietary sodium butyrate (SB) supplementation on the growth and immune function in the proximal intestine (PI), middle intestine (MI) and distal intestine (DI) of young grass carp (Ctenopharyngodon idella). The fish were fed one powdery sodium butyrate (PSB) diet (1000.0 mg kg(-1) diet) and five graded levels of microencapsulated sodium butyrate (MSB) diets: 0.0 (control), 500.0, 1000.0, 1500.0 and 2000.0 mg kg(-1) diet for 60 days. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila...
May 22, 2017: Fish & Shellfish Immunology
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