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https://www.readbyqxmd.com/read/29783985/the-doses-of-plasmid-backbone-plays-a-major-role-in-determining-the-hbv-clearance-in-hydrodynamic-injection-mouse-model
#1
Xian Wang, Jianmin Zhu, Yong Zhang, Yue Li, Tai Ma, Qun Li, Jiegou Xu, Long Xu
BACKGROUND: Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide, causing a major risk of liver disease and hepatocellular carcinoma (HCC). Many mouse models have been tried to establish HBV infection through injection with various HBV-containing plasmids. However, it is not well understood that different plasmids, all of which contain the similar HBV genome, even the same plasmids with different dose, results in opposite immune responses toward HBV. METHODS: In this study, we investigated the role of HBV-containing plasmid backbones and the HBcAg in determining the HBV persistence...
May 21, 2018: Virology Journal
https://www.readbyqxmd.com/read/29777988/insight-into-structural-requirements-for-selective-and-or-dual-cxcr3-and-cxcr4-allosteric-modulators
#2
Anja Kolarič, Urban Švajger, Tihomir Tomašič, Regine Brox, Theresa Frank, Nikola Minovski, Nuska Tschammer, Marko Anderluh
Based on the previously published pyrazolopyridine-based hit compound for which negative allosteric modulation of both CXCR3 and CXCR4 receptors was disclosed, we designed, synthesized and biologically evaluated a set of novel, not only negative, but also positive allosteric modulators with preserved pyrazolopyridine core. Compound 9e is a dual negative modulator, inhibiting G protein activity of both receptors. For CXCR4 receptor para-substituted aromatic group of compounds distinguishes between negative and positive modulation...
May 11, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29766641/tailoring-the-homing-capacity-of-human-tregs-for-directed-migration-to-sites-of-th1-inflammation-or-intestinal-regions
#3
Romy E Hoeppli, Katherine N MacDonald, Pascal Leclair, Vivian C W Fung, Majid Mojibian, Jana Gillies, Seyed M R Rahavi, Andrew I M Campbell, Sanjiv K Gandhi, Anne M Pesenacker, Gregor Reid, Chinten J Lim, Megan K Levings
Cell-based therapy with CD4+ FOXP3+ Regulatory T cells (Tregs) is a promising strategy to limit organ rejection and graft-versus-host disease. Ongoing clinical applications have yet to consider how human Tregs could be modified to direct their migration to specific inflammation sites and/or tissues for more targeted immunosuppression. We show here that stable, homing-receptor-tailored human Tregs can be generated from thymic Tregs isolated from pediatric thymus or adult blood. To direct migration to Th1-inflammatory sites, addition of IFN-γ and IL-12 during Treg expansion produced suppressive, epigenetically-stable CXCR3+ TBET+ FOXP3+ Th1-Tregs...
May 15, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29764680/the-parasite-derived-rov-asp-1-is-an-effective-antigen-sparing-cd4-t-cell-dependent-adjuvant-for-the-trivalent-inactivated-influenza-vaccine-and-functions-in-the-absence-of-myd88-pathway
#4
Sonia Jain, Parakkal Jovvian George, Wanyan Deng, Joseph Koussa, Kaela Parkhouse, Scott E Hensley, Jiu Jiang, Jie Lu, Zhuyun Liu, Junfei Wei, Bin Zhan, Maria Elena Bottazzi, Hao Shen, Sara Lustigman
Vaccination remains the most cost-effective biomedical approach for controlling influenza disease. In times of pandemics, however, these vaccines cannot be produced in sufficient quantities for worldwide use by the current manufacturing capacities and practices. What is needed is the development of adjuvanted vaccines capable of inducing an adequate or better immune response at a decreased antigen dose. Previously we showed that the protein adjuvant rOv-ASP-1 augments influenza-specific antibody titers and survival after virus challenge in both young adult and old-age mice when administered with the trivalent inactivated influenza vaccine (IIV3)...
May 12, 2018: Vaccine
https://www.readbyqxmd.com/read/29762848/cxcr3-mediates-chondrocyte-injury-through-regulating-nitric-oxide
#5
Z-C Yin, W-H Xiong, Q-J Pang
OBJECTIVE: As a common joint disease, osteoarthritis exhibits increasing trend in recent years. C-X-C motif chemokine receptor 3 (CXCR3) is a kind of chemokine with the characteristic of recruiting inflammatory cells. Its function in osteoarthritis has not been clarified. This study aims to explore the role of CXCR3 in cartilage injury by affecting unfolded protein response (UPR) pathway. PATIENTS AND METHODS: The sample was obtained from osteoarthritis patients to test CXCR3 expression by Real-time polymerase chain reaction (PCR)...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29760706/complement-opsonized-hiv-1-alters-cross-talk-between-dendritic-cells-and-natural-killer-nk-cells-to-inhibit-nk-killing-and-to-upregulate-pd-1-cxcr3-and-ccr4-on-t-cells
#6
Rada Ellegård, Mohammad Khalid, Cecilia Svanberg, Hanna Holgersson, Ylva Thorén, Mirja Karolina Wittgren, Jorma Hinkula, Sofia Nyström, Esaki M Shankar, Marie Larsson
Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29758330/human-liver-infiltrating-%C3%AE-%C3%AE-t-cells-are-composed-of-clonally-expanded-circulating-and-tissue-resident-populations
#7
Stuart Hunter, Carrie Willcox, Martin Davey, Sofya Kasatskaya, Hannah Jeffery, Dmitriy Chudakov, Ye Oo, Benjamin Willcox
BACKGROUND & AIM: γδ T-cells comprise a substantial proportion of tissue-associated lymphocytes. However, our current understanding of human γδ T-cells is primarily based on peripheral blood subsets, while the immunobiology of tissue-associated subsets remains largely unclear. METHODS: To address this, we characterised the TCR diversity, immunophenotype and function of human liver infiltrating γδ T-cells, focussing on the predominant tissue-associated Vδ2neg γδ subset, which is implicated in liver immunopathology...
May 11, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29752829/the-role-of-th1-th2-cytokines-played-in-regulation-of-specific-cd4-th1-cells-conversion-and-activation-during-inflammatory-reaction-of-chronic-obstructive-pulmonary-disease
#8
Jiaolin Sun, Ting Liu, Ying Yan, Kaikai Huo, Wenna Zhang, Hanhan Liu, Zhihong Shi
BACKGROUNDS: CD4 + Th1-CXCR3 signaling pathway may play a key role in Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to explore Th1/Th2 cytokines ratio differences of patients in different stages of COPD and to confirm the hypothesis that elastin exposure might serve as an antigen to initiate the stimulation of CD4 + Th1-CXCR3 immune inflammation pathway. METHODS: Patients of COPD in different stages and normal individuals were enrolled...
May 12, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29719539/natural-killer-cell-recruitment-to-the-lung-during-influenza-a-virus-infection-is-dependent-on-cxcr3-ccr5-and-virus-exposure-dose
#9
Lindsey E Carlin, Emily A Hemann, Zeb R Zacharias, Jonathan W Heusel, Kevin L Legge
Natural killer (NK) cells are vital components of the antiviral immune response, but their contributions in defense against influenza A virus (IAV) are not well understood. To better understand NK cell responses during IAV infections, we examined the magnitude, kinetics, and contribution of NK cells to immunity and protection during high- and low-dose IAV infections. Herein, we demonstrate an increased accumulation of NK cells in the lung in high-dose vs. low-dose infections. In part, this increase is due to the local proliferation of pulmonary NK cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29719256/sting-activating-adjuvants-elicit-a-th17-immune-response-and-protect-against-mycobacterium-tuberculosis-infection
#10
Erik Van Dis, Kimberly M Sogi, Chris S Rae, Kelsey E Sivick, Natalie H Surh, Meredith L Leong, David B Kanne, Ken Metchette, Justin J Leong, Jacob R Bruml, Vivian Chen, Kartoosh Heydari, Nathalie Cadieux, Tom Evans, Sarah M McWhirter, Thomas W Dubensky, Daniel A Portnoy, Sarah A Stanley
There are a limited number of adjuvants that elicit effective cell-based immunity required for protection against intracellular bacterial pathogens. Here, we report that STING-activating cyclic dinucleotides (CDNs) formulated in a protein subunit vaccine elicit long-lasting protective immunity to Mycobacterium tuberculosis in the mouse model. Subcutaneous administration of this vaccine provides equivalent protection to that of the live attenuated vaccine strain Bacille Calmette-Guérin (BCG). Protection is STING dependent but type I IFN independent and correlates with an increased frequency of a recently described subset of CXCR3-expressing T cells that localize to the lung parenchyma...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29713015/atherogenic-dyslipidemia-promotes-autoimmune-follicular-helper-t-cell-responses-via-il-27
#11
Heeju Ryu, Hoyong Lim, Garam Choi, Young-Jun Park, Minkyoung Cho, Hyeongjin Na, Chul Won Ahn, Young Chul Kim, Wan-Uk Kim, Sang-Hak Lee, Yeonseok Chung
The incidence of atherosclerosis is higher among patients with systemic lupus erythematosus (SLE); however, the mechanism by which an atherogenic environment affects autoimmunity remains unclear. We found that reconstitution of atherosclerosis-prone Apoe-/- and Ldlr-/- mice with bone marrow from lupus-prone BXD2 mice resulted in increased autoantibody production and glomerulonephritis. This enhanced disease was associated with an increase in CXCR3+ follicular helper T cells (TFH cells). TFH cells isolated from Apoe-/- mice had higher expression of genes associated with inflammatory responses and SLE and were more potent in inducing production of the immunoglobulin IgG2c...
April 30, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29712506/-express-spinal-cxcl9-and-cxcl11-are-not-involved-in-neuropathic-pain-despite-an-upregulation-in-the-spinal-cord-following-spinal-nerve-injury
#12
Xiao-Bo Wu, Li-Na He, Bao-Chun Jiang, Hui Shi, Xue-Qiang Bai, Wen-Wen Zhang, Yong-Jing Gao
Chemokines-mediated neuroinflammation in the spinal cord plays a critical role in the pathogenesis of neuropathic pain. Chemokine CXCL9, CXCL10 and CXCL11 have been identified as a same subfamily chemokine which bind to CXC chemokine receptor 3 (CXCR3) to exert functions. Our recent work found that CXCL10 is upregulated in spinal astrocytes after spinal nerve ligation (SNL), and acts on CXCR3 on neurons to contribute to central sensitization and neuropathic pain, but less is known about CXCL9 and CXCL11 in the maintenance of neuropathic pain...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29707158/differential-role-of-cxcr3-in-inflammation-and-colorectal-cancer
#13
REVIEW
Jessicca D Abron, Narendra P Singh, Angela E Murphy, Manoj K Mishra, Robert L Price, Mitzi Nagarkatti, Prakash S Nagarkatti, Udai P Singh
Chemokines (CXCR3) and their ligands (CXCL9, CXCL10, and CXCL11) exert exquisite control over T-cell trafficking and are critical for activation, differentiation and effector T cell function. CXCR3 is important for CD4 Th1 cells, CD8 effectors, memory cells, and for the function of natural killer and natural killer T cells. The presence of high cytotoxic CXCR3 ligand expression on CD8 T cells in colorectal cancerous tissue has been well documented in the past. CXCR3 and its ligands are differentially expressed at sites of inflammation and within the tumors...
April 3, 2018: Oncotarget
https://www.readbyqxmd.com/read/29705268/aberrant-detection-of-phenotypic-markers-in-chronic-lymphocytic-leukemia-cll-lymphocytes-following-cryopreservation
#14
Lauren A Thurgood, Karen M Lower, Cindy Macardle, Bryone J Kuss
The cryopreservation of peripheral blood mononuclear cells (PBMCs) is a routine research laboratory process, enabling long-term storage of primary patient blood samples. Retrospective analysis of these samples has the potential to identify markers which may associate with prognosis and response to treatment. In order to draw valid biological conclusions from this type of analysis, it is essential to ensure that any observed changes are directly related to the pathology of the disease rather than the preservation process itself...
April 26, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29698674/downregulation-in-helios-transcription-factor-signaling-is-associated-with-immune-dysfunction-in-blood-leukocytes-of-autistic-children
#15
Sheikh F Ahmad, Ahmed Nadeem, Mushtaq A Ansari, Saleh A Bakheet, Laila Yousef Al-Ayadhi, Sabry M Attia
Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder in which immunological imbalance has been suggested to be a major etiological component. Helios, a transcription factor, has been studied extensively in the context of human T cell regulation in health and disease, yet the role of Helios signaling has not been examined in children with ASD. In the present study, we investigated the production of Helios in CD4+ , CD8+ , and TIM-3+ , CXCR3+ cells in typically developing (TD) controls and children with ASD and in peripheral blood mononuclear cells (PBMCs)...
April 23, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29698357/t-cells-expressing-the-chemokine-receptor-cxcr3-localize-to-positive-patch-test-reaction-sites
#16
Jeffrey S Smith, Jutamas Suwanpradid, Amanda S MacLeod, Amber Reck Atwater
No abstract text is available yet for this article.
April 25, 2018: Dermatitis
https://www.readbyqxmd.com/read/29694256/associations-of-circulating-cxcr3-pd-1-cd4-t-cells-with-disease-activity-of-systemic-lupus-erythematosus
#17
Han Lei, Yang Xue, Yu Yiyun, Wan Weiguo, Lv Ling, Hejian Zou
OBJECTIVES: Which helper CD4+ T cell subset contributes to autoantibodies generation and severity of end-organ involvement in lupus patients remains to be explored. Our research aims to investigate the roles of circulating Tfh (cTfh) cell subsets and corresponding CXCR5- Th cells in lupus patients and their correlation with SLEDAI. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from blood of SLE patients as well as healthy donors. The proportion of Th cell Subsets classified from cell surface markers (CD45RO, CXCR5, CXCR3, CCR6, PD-1, ICOS, and CCR7) is detected by flow cytometry...
April 25, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29691471/baricitinib-induced-blockade-of-interferon-gamma-receptor-and-interleukin-6-receptor-for-the-prevention-and-treatment-of-graft-versus-host-disease
#18
Jaebok Choi, Matthew L Cooper, Karl Staser, Kidist Ashami, Kiran R Vij, Bing Wang, Lynne Marsala, Jessica Niswonger, Julie Ritchey, Bader Alahmari, Samuel Achilefu, Ikuo Tsunoda, Mark A Schroeder, John F DiPersio
The therapeutic benefits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are derived from the graft-versus-leukemia (GvL) effects of the procedure. There is a strong association between the GvL effects and graft-versus-host disease (GvHD), a major life-threatening complication of allo-HSCT. The limiting of GvHD while maintaining the GvL effect remains the goal of allo-HSCT. Therefore, identifying optimal therapeutic targets to selectively suppress GvHD while maintaining the GvL effects represents a significant unmet medical need...
April 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29690901/cxcl9-10-11-a-regulator-of-pd-l1-expression-in-gastric-cancer
#19
Chenlu Zhang, Zhi Li, Ling Xu, Xiaofang Che, Ti Wen, Yibo Fan, Ce Li, Shuo Wang, Yu Cheng, Xiaoxun Wang, Xiujuan Qu, Yunpeng Liu
BACKGROUND: Programmed death-ligand 1 (PD-L1) is an immunosuppressor that plays an important role in cancer treatments. Although majority of the studies demonstrated that PD-L1 expression was regulated by cellular intrinsic and extrinsic controls, and IFN-γ was a key molecule of extrinsic control, other studies imply that other cytokines play important roles in PD-L1 expression. In this study, we investigated the regulation of PD-L1 by chemokine signaling pathway in gastric cancer (GC) cells...
April 24, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29681802/expression-and-function-of-chemokines-cxcl9-11-in-micturition-pathways-in-cyclophosphamide-cyp-induced-cystitis-and-somatic-sensitivity-in-mice
#20
Michael Guo, Phat Chang, Eric Hauke, Beatrice M Girard, Katharine Tooke, Jacqueline Ojala, Susan M Malley, Harrison Hsiang, Margaret A Vizzard
Changes in urinary bladder function and somatic sensation may be mediated, in part, by inflammatory changes in the urinary bladder including the expression of chemokines. Male and female C57BL/6 mice were treated with cyclophosphamide (CYP; 75 mg/kg, 200 mg/kg, i.p.) to induce bladder inflammation (4 h, 48 h, chronic). We characterized the expression of CXC chemokines (CXCL9, CXCL10 and CXCL11) in the urinary bladder and determined the effects of blockade of their common receptor, CXCR3, at the level urinary bladder on bladder function and somatic (hindpaw and pelvic) sensation...
2018: Frontiers in Systems Neuroscience
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