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https://www.readbyqxmd.com/read/29024606/role-of-the-tslp-dc-ox40l-pathway-in-asthma-pathogenesis-and-airway-inflammation-in-mice
#1
Shuang Feng, Li Zhang, Xu-Hua Bian, Ying Luo, Guang-Hui Qin, Rui-Ming Shi
This study aims to explore the effect of the TSLP/DC/OX40L pathway in asthma pathogenesis and airway inflammation in mice. Sixty-five male BALF/c mice were divided into the control, asthma, IgG + asthma (IgG, 500 g/500 l, intratracheal injection of 50 l each time), LY294002 (OX40L inhibitor) + asthma (intratracheal injection of 2 mg/kg LY294002), and anti-TSLP + asthma (intratracheal injection of 500 ug/500 l TSLP antibody, 50 l each time) groups. ELISA was applied to measure the serum levels of IgE, ovalbumin (OVA)-sIgE, interleukin-4 (IL-4), IL-5, IL-13 and interferon-γ (IFN-γ), flow cytometry was employed to detect Treg cells and dendritic cell (DC) and lymphopoiesis...
October 12, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28974950/exploring-synergy-in-combinations-of-tumor-derived-vaccines-that-harbor-4-1bbl-ox40l-and-gm-csf
#2
Andrea J Manrique-Rincón, Camila M Beraldo, Jessica M Toscaro, Marcio C Bajgelman
Recent studies have demonstrated that combination of modulatory immune strategies may potentiate tumor cell elimination. Most strategies rely on the use of monoclonal antibodies that can block cell surface receptors to overcome tumor-induced immunosuppression or acting as costimulatory ligands to boost activation of T cells. In this study, we evaluate the use of combinations of genetically modified tumor-derived cell lines that harbor the costimulatory T cell ligands 4-1BB ligand, OX40L, and the cytokine GM-CSF...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#3
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28929455/role-of-mast-cells-in-regulation-of-t-cell-responses-in-experimental-and-clinical-settings
#4
REVIEW
Daniel Elieh Ali Komi, Korneel Grauwet
Mast cells secrete a wide spectrum of stored or newly synthesized pro-inflammatory, anti-inflammatory, and/or immunosuppressive mediators and express several costimulatory and inhibitory surface molecules. Mast cells finely tune activities of T cells, B cells, and regulatory cells and effectively contribute to the development of different T cell-associated responses by influencing their recruitment, activation, proliferation, and differentiation. The interaction between mast cells and T cells, with regard to cellular functionality and immune responses, can be assessed in both activating and inhibitory regulations...
September 19, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28878335/systemic-lupus-erythematosus-ox40l-expressing-b-cells-promote-sle
#5
Jessica McHugh
No abstract text is available yet for this article.
October 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28818832/b-cell-ox40l-supports-t-follicular-helper-cell-development-and-contributes-to-sle-pathogenesis
#6
Andrea Cortini, Ursula Ellinghaus, Talat H Malik, Deborah S Cunninghame Graham, Marina Botto, Timothy James Vyse
OBJECTIVES: TNFSF4 (encodes OX40L) is a susceptibility locus for systemic lupus erythematosus (SLE). Risk alleles increase TNFSF4 expression in cell lines, but the mechanism linking this effect to disease is unclear, and the OX40L-expressing cell types mediating the risk are not clearly established. Blockade of OX40L has been demonstrated to reduce disease severity in several models of autoimmunity, but not in SLE. We sought to investigate its potential therapeutic role in lupus. METHODS: We used a conditional knockout mouse system to investigate the function of OX40L on B and T lymphocytes in systemic autoimmunity...
August 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28747670/pkc-%C3%B1-is-dispensable-for-ox40l-induced-tcr-independent-treg-proliferation-but-contributes-by-enabling-il-2-production-from-effector-t-cells
#7
Khaled Alharshawi, Alejandra Marinelarena, Prabhakaran Kumar, Osama El-Sayed, Palash Bhattacharya, Zuoming Sun, Alan L Epstein, Ajay V Maker, Bellur S Prabhakar
We have previously shown that OX40L/OX40 interaction is critical for TCR-independent selective proliferation of Foxp3(+) Tregs, but not Foxp3(-) effector T-cells (Teff), when CD4(+) T-cells are co-cultured with GM-CSF derived bone marrow dendritic cells (G-BMDCs). Events downstream of OX40L/OX40 interaction in Tregs responsible for this novel mechanism are not understood. Earlier, OX40L/OX40 interaction has been shown to stimulate CD4(+) T-cells through the formation of a signalosome involving TRAF2/PKC-Ѳ leading to NF-kB activation...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696253/the-ox40-ox40-ligand-pathway-promotes-pathogenic-th-cell-responses-plasmablast-accumulation-and-lupus-nephritis-in-nzb-w-f1-mice
#8
Jonathan Sitrin, Eric Suto, Arthur Wuster, Jeffrey Eastham-Anderson, Jeong M Kim, Cary D Austin, Wyne P Lee, Timothy W Behrens
Ox40 ligand (Ox40L) locus genetic variants are associated with the risk for systemic lupus erythematosus (SLE); however, it is unclear how Ox40L contributes to SLE pathogenesis. In this study, we evaluated the contribution of Ox40L and its cognate receptor, Ox40, using in vivo agonist and antagonist approaches in the NZB × NZW (NZB/W) F1 mouse model of SLE. Ox40 was highly expressed on several CD4 Th cell subsets in the spleen and kidney of diseased mice, and expression correlated with disease severity. Treatment of aged NZB/W F1 mice with agonist anti-Ox40 mAbs potently exacerbated renal disease, which was accompanied by activation of kidney-infiltrating T cells and cytokine production...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28599652/regulatory-t-cells-in-multiple-sclerosis-and-myasthenia-gravis
#9
REVIEW
K M Danikowski, S Jayaraman, B S Prabhakar
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs)...
June 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28566332/oncolytic-adenovirus-and-tumor-targeting-immune-modulatory-therapy-improve-autologous-cancer-vaccination
#10
Hong Jiang, Yisel Rivera-Molina, Candelaria Gomez-Manzano, Karen Clise-Dwyer, Laura Bover, Luis M Vence, Ying Yuan, Frederick F Lang, Carlo Toniatti, Mohammad B Hossain, Juan Fueyo
Oncolytic viruses selectively lyse tumor cells, disrupt immunosuppression within the tumor, and reactivate antitumor immunity, but they have yet to live up to their therapeutic potential. Immune checkpoint modulation has been efficacious in a variety of cancer with an immunogenic microenvironment, but is associated with toxicity due to nonspecific T-cell activation. Therefore, combining these two strategies would likely result in both effective and specific cancer therapy. To test the hypothesis, we first constructed oncolytic adenovirus Delta-24-RGDOX expressing the immune costimulator OX40 ligand (OX40L)...
July 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28493549/transcription-factor-rbp-j-mediated-signalling-regulates-basophil-immunoregulatory-function-in-mouse-asthma-model
#11
Shuo-Yao Qu, Ya-Long He, Jian Zhang, Chang-Gui Wu
Basophils (BA) play an important role in the promotion of aberrant T helper type 2 (Th2) immune responses in asthma. It is not only the effective cell, but also modulates the initiation of Th2 immune responses. We earlier demonstrated that Notch signalling regulates the biological function of BAin vitro. However, whether this pathway plays the same role in vivo is not clear. The purpose of the present study was to investigate the effect of Notch signalling on BA function in the regulation of allergic airway inflammation in a murine model of asthma...
September 2017: Immunology
https://www.readbyqxmd.com/read/28420813/establishment-of-cell-lines-from-adult-t-cell-leukemia-cells-dependent-on-negatively-charged-polymers
#12
Yoshitoyo Kagami, Susumu Uchiyama, Harumi Kato, Yasutaka Okada, Masao Seto, Tomohiro Kinoshita
Growing adult T-cell leukemia/lymphoma (ATLL) cells in vitro is difficult. Here, we examined the effects of static electricity in the culture medium on the proliferation of ATLL cells. Six out of 10 ATLL cells did not proliferate in vitro and thus had to be cultured in a medium containing negatively charged polymers. In the presence of poly-γ-glutamic acid (PGA) or chondroitin sulfate (CDR), cell lines (HKOX3-PGA, HKOX3-CDR) were established from the same single ATLL case using interleukin (IL)-2, IL-4, and feeder cells expressing OX40L (OX40L(+)HK)...
July 5, 2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28369782/immune-checkpoint-proteins-exploring-their-therapeutic-potential-to-regulate-atherosclerosis
#13
REVIEW
A C Foks, J Kuiper
The immune system provides a large variety of immune checkpoint proteins, which involve both costimulatory and inhibitory proteins. Costimulatory proteins can promote cell survival, cell cycle progression and differentiation to effector and memory cells, whereas inhibitory proteins terminate these processes to halt ongoing inflammation. Immune checkpoint proteins play a pivotal role in atherosclerosis by regulating the activation and proliferation of various immune and non-immune cells, such as T-cells, macrophages and platelets...
March 30, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28332559/the-immunogenetics-of-narcolepsy-associated-with-a-h1n1-pdm09-vaccination-pandemrix-supports-a-potent-gene-environment-interaction
#14
MULTICENTER STUDY
I L Bomfim, F Lamb, K Fink, A Szakács, A Silveira, L Franzén, V Azhary, M Maeurer, N Feltelius, N Darin, T Hallböök, L Arnheim-Dahlström, I Kockum, T Olsson
The influenza A(H1N1)pdm09 vaccination campaign from 2009 to 2010 was associated with a sudden increase in the incidence of narcolepsy in several countries. Narcolepsy with cataplexy is strongly associated with the human leukocyte antigen (HLA) class II DQB1*06:02 allele, and protective associations with the DQB1*06:03 allele have been reported. Several non-HLA gene loci are also associated, such as common variants of the T-cell receptor-α (TRA), the purinergic receptor P2RY11, cathepsin H (CTSH) and TNFSF4/OX40L/CD252...
March 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28320444/ox40-signaling-is-involved-in-the-autoactivation-of-cd4-cd28-t-cells-and-contributes-to-the-pathogenesis-of-autoimmune-arthritis
#15
Juean Jiang, Cuiping Liu, Mi Liu, Yu Shen, Xiaohan Hu, Qin Wang, Jian Wu, Min Wu, Qi Fang, Xueguang Zhang
BACKGROUND: CD4(+)CD28(-) T cells exhibit autoreactive potential in autoimmune disorders, including rheumatoid arthritis (RA). It is not well known which costimulator functions as an alternative second signal in the activation of this subset after CD28 expression is downregulated. Tumor necrosis factor receptor superfamily member OX40 is a key costimulator in the activation of T cells. The aim of this study was to investigate the costimulatory effects of OX40 on CD4(+)CD28(-) T cells in autoimmune arthritis...
March 21, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28289708/interruption-of-ox40l-signaling-prevents-costimulation-blockade-resistant-allograft-rejection
#16
William H Kitchens, Ying Dong, David V Mathews, Cynthia P Breeden, Elizabeth Strobert, Maria E Fuentes, Christian P Larsen, Mandy L Ford, Andrew B Adams
The potential of costimulation blockade to serve as a novel transplant immunosuppression strategy has been explored for over 20 years, culminating in the recent clinical approval of belatacept for renal transplant patients. Despite improving long-term graft function and survival compared with calcineurin inhibitors, clinical acceptance of belatacept has been hindered by elevated rates of acute rejection. We examined the signaling pathways required to activate costimulation blockade-resistant alloreactive T cells and identified the OX40/OX40L secondary costimulatory pathway as a promising target...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28287273/novel-monoclonal-treatments-in-severe-asthma
#17
Howraman Meteran, Hanieh Meteran, Celeste Porsbjerg, Vibeke Backer
AIM: To provide a general overview of the current biological treatments and discuss their potential anti-asthmatic effects. DATA SOURCES: We reviewed articles in PubMed found using the search words "Asthma/therapy AND antibodies, monoclonal/therapeutic use AND cytokines." STUDY SELECTIONS: Only articles published in English since 2000 were considered. The search identified 29 studies; 8 additional studies were found by hand search, generating 37 studies...
March 13, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28214951/inhibition-of-jak-stat-pathway-restrains-tslp-activated-dendritic-cells-mediated-inflammatory-t-helper-type-2-cell-response-in-allergic-rhinitis
#18
Zhaohui Shi, Weihong Jiang, Min Wang, Xiaocheng Wang, Xiaoyuan Li, Xiaodong Chen, Li Qiao
Thymic stromal lymphopoietin (TSLP) has recently been implicated as a key molecule for initiating allergic rhinitis (AR) at the cell-dendritic cell (DC) interface. Previous studies demonstrated that TSLP activated DCs to express more OX40 ligand (OX40L), which is associated with the initiation of T helper type 2 (Th2) cell responses. STAT phosphorylation has been reported to be promoted by TSLP. Thus, we investigated if the JAK/STAT pathway inhibitor CYT387 could affect TSLP-DC-mediated Th2 cell response in naive T cell and AR mice model...
February 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28132739/the-th2-polarizing-function-of-atopic-interleukin-17-receptor-b-positive-dendritic-cells-up-regulated-by-lipopolysaccharide
#19
Rui Zheng, Feng-Hong Chen, Wen-Xiang Gao, Dan Wang, Qin-Tai Yang, Kai Wang, Yin-Yan Lai, Jie Deng, Li-Jie Jiang, Yue-Qi Sun, Jian-Bo Shi
BACKGROUND: Recent studies suggest that epithelial cell (EC)-derived cytokines contribute to allergic airway disease exacerbation. OBJECTIVE: To confirm our hypothesis that atopic dendritic cells (DCs) are activated to up-regulate the receptors of cytokines that mainly derived from ECs and enhance TH2 responses. METHODS: The expressions of interleukin 17 receptor B (IL-17RB) (IL-25 receptor), membrane-bound ST2 (IL-33 receptor), thymic stromal lymphopoietin receptor (TSLPR), granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), and several functional markers on CD1c(+) monocyte-derived DCs (mo-DCs) were detected by flow cytometry...
April 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28086903/negative-immune-factors-might-predominate-local-tumor-immune-status-and-promote-carcinogenesis-in-cervical-carcinoma
#20
Minyi Zhao, Yang Li, Xing Wei, Qian Zhang, Hongran Jia, Shimin Quan, Di Cao, Li Wang, Ting Yang, Juan Zhao, Meili Pei, Sijuan Tian, Yang Yu, Yanping Guo, Xiaofeng Yang
BACKGROUND: The disequilibrium of local immune microenvironment is an essential element during tumorigenesis. METHOD: By conducting real-time polymerase chain reaction, we identified the mRNA level of immune factors, FoxP3 (forkhead box protein P3), CCL22/CCR4 (chemokine (C-C motif) ligand 22/CC chemokine receptor 4), OX40L/OX40 (tumor necrosis factor superfamily member 4/tumor necrosis factor receptor superfamily member 4) and Smad3 (SMAD family member 3) in neoplastic foci and its periphery tissues from 30 cases of squamous cervical carcinoma and 20 cases of normal cervix...
January 13, 2017: Virology Journal
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