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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
#1
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
#2
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...
January 26, 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
#3
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
https://www.readbyqxmd.com/read/28069723/a-novel-murine-gitr-ligand-fusion-protein-induces-antitumor-activity-as-a-monotherapy-which-is-further-enhanced-in-combination-with-an-ox40-agonist
#4
Rebecca Leyland, Amanda Watkins, Kathy Mulgrew, Nicholas Holoweckyj, Lisa Bamber, Natalie J Tigue, Emily Offer, John Andrews, Li Yan, Stefanie Mullins, Michael D Oberst, Jane Coates Ulrichsen, David A Leinster, Kelly A McGlinchey, Lesley Young, Michelle Morrow, Scott A Hammond, Philip R Mallinder, Athula Herath, Ching Ching Leow, Robert W Wilkinson, Ross Stewart
PURPOSE: To generate and characterize a murine GITR ligand fusion protein (mGITRL-FP) designed to maximize valency and the potential to agonize the GITR receptor for cancer immunotherapy. EXPERIMENTAL DESIGN: The EC50 value of the mGITRL-FP was compared to an anti-GITR antibody in an in vitro agonistic cell based reporter assay. We assessed the impact of dose, schedule and Fc isotype on antitumor activity and T-cell modulation in the CT26 tumor model. The activity of the mGITRL-FP was compared to an agonistic murine OX40L-FP targeting OX40, in CT26 and B16F10-Luc2 tumor models...
January 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28045060/soluble-ox40l-and-jag1-induce-selective-proliferation-of-functional-regulatory-t-cells-independent-of-canonical-tcr-signaling
#5
Prabhakaran Kumar, Khaled Alharshawi, Palash Bhattacharya, Alejandra Marinelarena, Christine Haddad, Zuoming Sun, Shigeru Chiba, Alan L Epstein, Bellur S Prabhakar
Regulatory T-cells (Tregs) play a pivotal role in maintaining peripheral tolerance. Increasing Treg numbers/functions has been shown to ameliorate autoimmune diseases. However, common Treg expansion approaches use T-Cell Receptor (TCR)-mediated stimulation which also causes proliferation of effector T-cells (Teff). To overcome this limitation, purified patient-specific Tregs are expanded ex vivo and transfused. Although promising, this approach is not suitable for routine clinical use. Therefore, an alternative approach to selectively expand functional Tregs in vivo is highly desired...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27939673/perinatal-activation-of-the-interleukin-33-pathway-promotes-type-2-immunity-in-the-developing-lung
#6
Ismé M de Kleer, Mirjam Kool, Marjolein J W de Bruijn, Monique Willart, Justine van Moorleghem, Martijn J Schuijs, Maud Plantinga, Rudi Beyaert, Emily Hams, Padraic G Fallon, Hamida Hammad, Rudi W Hendriks, Bart N Lambrecht
Allergic disease originates in early life and polymorphisms in interleukin-33 gene (IL33) and IL1RL1, coding for IL-33R and decoy receptor sST2, confer allergy risk. Early life T helper 2 (Th2) cell skewing and allergy susceptibility are often seen as remnants of feto-maternal symbiosis. Here we report that shortly after birth, innate lymphoid type 2 cells (ILC2s), eosinophils, basophils, and mast cells spontaneously accumulated in developing lungs in an IL-33-dependent manner. During the phase of postnatal lung alveolarization, house dust mite exposure further increased IL-33, which boosted cytokine production in ILC2s and activated CD11b(+) dendritic cells (DCs)...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27905107/co-operative-suppression-of-inflammatory-responses-in-human-dendritic-cells-by-plant-proanthocyanidins-and-products-from-the-parasitic-nematode-trichuris-suis
#7
Andrew R Williams, Elsenoor J Klaver, Lisa C Laan, Aina Ramsay, Christos Fryganas, Rolf Difborg, Helene Kringel, Jess D Reed, Irene Mueller-Harvey, Søren Skov, Irma van Die, Stig M Thamsborg
Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesized that PAC may suppress lipopolysaccharide (LPS) -induced responses in human DCs and subsequent T helper type 1 (Th1) -type responses in naive T cells. Moreover, we proposed that, because DCs are likely to be exposed to multiple stimuli, the activity of PAC may synergise with other bioactive molecules that have anti-inflammatory activity, e...
March 2017: Immunology
https://www.readbyqxmd.com/read/27896636/tnf-superfamily-cytokines-in-the-promotion-of-th9-differentiation-and-immunopathology
#8
REVIEW
Françoise Meylan, Richard M Siegel
The tumor necrosis factor (TNF) receptors and their corresponding cytokine ligands have been implicated in many aspects of the biology of immune functions. TNF receptors have key roles during various stages of T cell homeostasis. Many of them can co-stimulate lymphocyte proliferation and cytokine production. Additionally, several TNF cytokines can regulate T cell differentiation, including promoting Th1, Th2, Th17, and more recently the newly described Th9 subset. Four TNF family cytokines have been identified as regulators for IL-9 production by T cells...
November 28, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27895177/ox40-cooperates-with-icos-to-amplify-follicular-th-cell-development-and-germinal-center-reactions-during-infection
#9
Vikas Tahiliani, Tarun E Hutchinson, Georges Abboud, Michael Croft, Shahram Salek-Ardakani
Cognate interactions between T follicular helper (Tfh) cells and B cells are essential for promoting protective Ab responses. Whereas costimulatory receptors such as ICOS are accepted as being important for the induction of Tfh cell fate decision, other molecules may play key roles in amplifying or maintaining the Tfh phenotype. In this study, with vaccinia virus infection in mice, we show that OX40 was expressed on Tfh cells that accumulated at the T/B borders in the white pulp of the spleen and that OX40-dependent signals directly shaped the magnitude and quality of the their response to viral Ags...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27878248/immunomodulatory-effects-of-ox40ig-gene-modified-adipose-tissue-derived-mesenchymal-stem-cells-on-rat-kidney-transplantation
#10
Tao Liu, Yue Zhang, Zhongyang Shen, Xunfeng Zou, Xiaobo Chen, Li Chen, Yuliang Wang
Recent studies have suggested that adipose tissue-derived mesenchymal stem cell (ADSC) therapy and OX40 costimulation blockade are two immunomodulatory strategies used to suppress the immune response to alloantigens. However, relatively little has been reported regarding the immunomodulatory potential of the abilityof these two strategies to synergize. Thus, in the present study, we aimed to investigate OX40-Ig fusion protein (OX40Ig) expression in ADSCs and to validate their more potent immunosuppressive activity in preventing renal allograft rejection...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27708417/critical-role-of-transcription-factor-pu-1-in-the-function-of-the-ox40l-tnfsf4-promoter-in-dendritic-cells
#11
Takuya Yashiro, Mutsuko Hara, Hideoki Ogawa, Ko Okumura, Chiharu Nishiyama
PU.1 is a hematopoietic lineage-specific transcription factor belonging to the Ets family. We investigated the role of PU.1 in the expression of OX40L in dendritic cells (DCs), because the regulatory mechanism of cell type-specific expression of OX40L, which is mainly restricted to antigen-presenting cells, is largely unknown despite the critical involvement in Th2 and Tfh development. PU.1 knockdown decreased the expression of OX40L in mouse DCs. Chromatin immunoprecipitation (ChIP) assays demonstrated that PU...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27519474/tnfsf4-polymorphisms-are-associated-with-systemic-lupus-erythematosus-in-the-malaysian-population
#12
K H Chua, Y Y Ooh, H C Chai
Tumour necrosis factor superfamily 4 (TNFSF4) gene has been reported to be associated with systemic lupus erythematosus (SLE) susceptibility due to its encoding for OX40L protein that can increase autoantibody production and cause imbalance of T-cell proliferation. The purpose of this study was to investigate the association of TNFSF4 rs2205960, rs1234315, rs8446748 and rs704840 with SLE in the Malaysian population. A total of 476 patients with SLE and 509 healthy controls were recruited. Real-time polymerase chain reaction (PCR) was applied to genotype the selected single nucleotide polymorphisms (SNPs)...
October 2016: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/27492902/dectin-1-activated-dendritic-cells-trigger-potent-antitumour-immunity-through-the-induction-of-th9-cells
#13
Yinghua Zhao, Xiao Chu, Jintong Chen, Ying Wang, Sujun Gao, Yuxue Jiang, Xiaoqing Zhu, Guangyun Tan, Wenjie Zhao, Huanfa Yi, Honglin Xu, Xingzhe Ma, Yong Lu, Qing Yi, Siqing Wang
Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering protective antifungal Th17 responses. However, whether dectin-1 directs DCs to prime antitumour Th9 cells remains unclear. Here, we show that DCs activated by dectin-1 agonists potently promote naive CD4(+) T cells to differentiate into Th9 cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polarizing capability in response to dectin-1 agonist curdlan. Notably, dectin-1 stimulation of DCs upregulates TNFSF15 and OX40L, which are essential for dectin-1-activated DC-induced Th9 cell priming...
2016: Nature Communications
https://www.readbyqxmd.com/read/27364122/gp96-ig-costimulator-ox40l-icosl-or-4-1bbl-combination-vaccine-improves-t-cell-priming-and-enhances-immunity-memory-and-tumor-elimination
#14
George Fromm, Suresh de Silva, Louise Giffin, Xin Xu, Jason Rose, Taylor H Schreiber
T-cell costimulation typically occurs in a defined microenvironment that is not recapitulated by agonistic antibody therapy. To deliver such stimulation under more favorable conditions, we investigated whether an allogeneic cell-based vaccine that secreted Fc-OX40L, Fc-ICOSL, or Fc-4-1BBL would activate and expand T cells comparably with systemically administered agonist antibodies. Among these costimulators, locally secreted Fc-OX40L provided superior priming of antigen-specific CD8(+) T cells, compared with combinations with OX40 antibodies or vaccine alone...
September 2, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27357256/connective-tissue-diseases-ox40l-inhibition-blocks-tissue-fibrosis
#15
Joanna Collison
No abstract text is available yet for this article.
August 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27343171/the-effect-of-dermatophagoides-pteronyssinus-group-7-allergen-der-p-7-on-dendritic-cells-and-its-role-in-t-cell-polarization
#16
Jaw-Ji Tsai, Hsin-Chieh Wang, Chih-Liang Chiu, En-Chih Liao
The innate signaling pathway for Th2 immunity activated by inhaled allergens has not been well defined. Dendritic cells (DCs) can use their innate pattern-recognition Toll-like receptors and C-type lectin receptors to generate innate immunity and influence adaptive responses. The aim of this study was to investigate the glycoform of Dermatophagoides pteronyssinus group 7 allergen (Der p 7) and its functional interaction with dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)...
November 2016: Immunobiology
https://www.readbyqxmd.com/read/27323820/co-expression-of-cd40l-with-cd70-or-ox40l-increases-b-cell-viability-and-antitumor-efficacy
#17
Chang-Ae Shin, Hyun-Woo Cho, A-Ri Shin, Hyun-Jung Sohn, Hyun-Il Cho, Tai-Gyu Kim
Activated B-cells are a promising alternative source of antigen-presenting cells. They can generally be obtained in sufficient numbers for clinical use, but in most instances produce weak immune responses and therapeutic effects that are suboptimal for use in therapeutic cancer vaccines. To improve the immunogenic potency and therapeutic efficacy of B-cell-based vaccines, ex vivo-activated B-cells were transduced with recombinant lentiviruses in order to express additional costimulatory ligands-CD40L, CD70, OX40L, or 4-1BBL-either individually or in pairs (CD70/CD40L, OX40L/CD40L, or 4-1BBL/CD40L)...
July 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27298374/ox40l-blockade-protects-against-inflammation-driven-fibrosis
#18
Muriel Elhai, Jérôme Avouac, Anna Maria Hoffmann-Vold, Nadira Ruzehaji, Olivia Amiar, Barbara Ruiz, Hassina Brahiti, Matthieu Ponsoye, Maxime Fréchet, Anne Burgevin, Sonia Pezet, Jérémy Sadoine, Thomas Guilbert, Carole Nicco, Hisaya Akiba, Vigo Heissmeyer, Arun Subramaniam, Robert Resnick, Øyvind Molberg, André Kahan, Gilles Chiocchia, Yannick Allanore
Treatment for fibrosis represents a critical unmet need, because fibrosis is the leading cause of death in industrialized countries, and there is no effective therapy to counteract the fibrotic process. The development of fibrosis relates to the interplay between vessel injury, immune cell activation, and fibroblast stimulation, which can occur in various tissues. Immunotherapies have provided a breakthrough in the treatment of immune diseases. The glycoprotein OX40-OX40 ligand (OX40L) axis offers the advantage of a targeted approach to costimulatory signals with limited impact on the whole immune response...
July 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27245356/age-dependent-divergent-effects-of-ox40l-treatment-on-the-development-of-diabetes-in-nod-mice
#19
Christine S Haddad, Palash Bhattacharya, Khaled Alharshawi, Alejandra Marinelarena, Prabhakaran Kumar, Osama El-Sayed, Hatem A Elshabrawy, Alan L Epstein, Bellur S Prabhakar
Earlier, we have shown that GM-CSF derived bone marrow (BM) dendritic cells (G-BMDCs) can expand Foxp3(+) regulatory T-cells (Tregs) through a TCR-independent, but IL-2 dependent mechanism that required OX40L/OX40 interaction. While some reports have shown suppression of autoimmunity upon treatment with an OX40 agonist, others have shown exacerbation of autoimmune disease instead. To better understand the basis for these differing outcomes, we compared the effects of OX40L treatment in 6-week-old pre-diabetic and 12-week-old near diabetic NOD mice...
August 2016: Autoimmunity
https://www.readbyqxmd.com/read/27203665/soluble-ox40l-favors-tumor-rejection-in-ct26-colon-carcinoma-model
#20
Ekaterina O Serebrovskaya, Diana V Yuzhakova, Alina P Ryumina, Irina N Druzhkova, George V Sharonov, Alexey A Kotlobay, Elena V Zagaynova, Sergey A Lukyanov, Marina V Shirmanova
OX40 receptor-expressing regulatory T cells (Tregs) populate tumors and suppress a variety of immune cells, posing a major obstacle for cancer immunotherapy. Different ways to functionally inactivate Tregs by triggering OX40 receptor have been suggested, including anti-OX40 antibodies and Fc:OX40L fusion proteins. To investigate whether the soluble extracellular domain of OX40L (OX40Lexo) is sufficient to enhance antitumor immune response, we generated an OX40Lexo-expressing CT26 colon carcinoma cell line and studied its tumorigenicity in immunocompetent BALB/c and T cell deficient nu/nu mice...
August 2016: Cytokine
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