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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
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
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
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
Joanna Collison
No abstract text is available yet for this article.
August 2016: Nature Reviews. Rheumatology
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
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)...
June 15, 2016: Oncotarget
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
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
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
Soledad Gori, Mónica Vermeulen, Federico Remes-Lenicov, Carolina Jancic, Walter Scordo, Ana Ceballos, Nadia Towstyka, Yesica Bestach, Carolina Belli, Florencia Sabbione, Jorge Geffner, Gabriela Salamone
BACKGROUND: A growing body of research shows a reciprocal regulation between the neural and immune systems. Acetylcholine (ACh) is the most important parasympathetic neurotransmitter and increasing evidence indicates that it is able to modulate the immune response. Interestingly, in recent years it has become clear that immune cells express a non-neuronal cholinergic system, which is stimulated in the course of inflammatory processes. We have previously shown that dendritic cells (DC) express muscarinic receptors, as well as the enzymes responsible for the synthesis and degradation of ACh...
May 3, 2016: Allergy
Mariona Camps-Bossacoma, Mar Abril-Gil, Sandra Saldaña-Ruiz, Àngels Franch, Francisco J Pérez-Cano, Margarida Castell
Cocoa powder, a rich source of polyphenols, has shown immunomodulatory properties in both the intestinal and systemic immune compartments of rats. The aim of the current study was to establish the effect of a cocoa diet in a rat oral sensitization model and also to gain insight into the mesenteric lymph nodes (MLN) activities induced by this diet. To achieve this, three-week-old Lewis rats were fed either a standard diet or a diet with 10% cocoa and were orally sensitized with ovalbumin (OVA) and with cholera toxin as a mucosal adjuvant...
2016: Nutrients
Qin Wang, Bi-Min Shi, Fang Xie, Zhao-Yang Fu, Yong-Jing Chen, Jing-Nan An, Yu Ma, Cui-Ping Liu, Xue-Kun Zhang, Xue-Guang Zhang
OX40/OX40L pathway plays a very important role in the antigen priming T cells and effector T cells. In the present study, we aimed to examine the involvement of OX40/OX40L pathway in the activation of autoreactive T cells in patients with Grave's disease (GD). We found that OX40 and OX40L were constitutively coexpressed on peripheral CD4(+) T cells from GD patients using flow cytometry analysis. The levels of OX40 and OX40L coexpression on CD4(+) T cells were shown to be correlated with TRAbs. Cell proliferation assay showed that blocking OX40/OX40L signal inhibited T cell proliferation and survival, which suggested that OX40/OX40L could enhance CD4(+) T cell proliferation and maintain their long-term survival in GD by self-enhancing loop of T cell activation independent of APCs...
July 15, 2016: Molecular and Cellular Endocrinology
Fei Li, Yuping Wang, Lihui Lin, Juan Wang, Hui Xiao, Jia Li, Xia Peng, Huirong Dai, Li Li
Exosomes are nanovesicles released by different cell types, such as dendritic cells (DCs), mast cells (MCs), and tumor cells. Exosomes of different origin play a role in antigen presentation and modulation of immune response to infectious disease. In this study, we demonstrate that mast cells and CD4(+) T cells colocated in peritoneal lymph nodes from BALB/c mouse. Further, bone marrow-derived mast cells (BMMCs) constitutively release exosomes, which express CD63 and OX40L. BMMC-exosomes partially promoted the proliferation of CD4(+) T cells...
2016: Journal of Immunology Research
Qingxiang Meng, Xiaolong Liu, Peng Li, Long He, Jinghua Xie, Xionghui Gao, Xiaozhong Wu, Fang Su, Yong Liang
BACKGROUND: This study aimed to investigate the clinical efficacy of sublingual immunotherapy (SLIT) with house dust mite (HDM) extract and to examine T helper 2 (Th2)-type immune responses mediated by the thymic stromal lymphopoietin (TSLP-OX40L) signaling pathway in patients with moderate to severe allergic rhinitis (AR) after 12-month HDM SLIT. METHODS: Forty-six cases of HDM-sensitized patients with persistent AR in southern China were enrolled in this study...
August 2016: International Forum of Allergy & Rhinology
Taizou Hirano, Toshiaki Kikuchi, Naoki Tode, Arif Santoso, Mitsuhiro Yamada, Yoshiya Mitsuhashi, Riyo Komatsu, Takeshi Kawabe, Takeshi Tanimoto, Naoto Ishii, Yuetsu Tanaka, Hidekazu Nishimura, Toshihiro Nukiwa, Akira Watanabe, Masakazu Ichinose
Influenza virus epidemics potentially cause pneumonia, which is responsible for much of the mortality due to the excessive immune responses. The role of costimulatory OX40-OX40 ligand (OX40L) interactions has been explored in the non-infectious pathology of influenza pneumonia. Here, we describe a critical contribution of OX40L to infectious pathology, with OX40L deficiency, but not OX40 deficiency, resulting in decreased susceptibility to influenza viral infection. Upon infection, bronchiolar progenitors increase in number for repairing the influenza-damaged epithelia...
2016: EMBO Molecular Medicine
Jolien Suurmond, Annemarie L Dorjée, Tom W J Huizinga, René E M Toes
Mast cells are innate immune cells usually residing in peripheral tissues, where they are likely to activate T-cell responses. Similar to other myeloid immune cells, mast cells can function as antigen-presenting cells. However, little is known about the capacity of human mast cells to costimulate CD4(+) T cells. Here, we studied the T-cell stimulatory potential of human mast cells. Peripheral blood derived mast cells were generated and cocultured with isolated CD4(+) T cells. In the presence of T-cell receptor triggering using anti-CD3, mast cells promoted strong proliferation of T cells, which was two- to fivefold stronger than the "T-cell promoting capacity" of monocytes...
May 2016: European Journal of Immunology
Yi-xiang Wang, Na An, Xiang-ying Ouyang
OBJECTIVE: To investigate molecular mechanism involved in nicotine in combination with Porphyromonas gingivalis (P.g) caused monocyte-endothelial cell adhesion. METHODS: The effect of nicotine, P.g-lipopolysaccharide (P.g-LPS) and their combination on the proliferation of U937 cells was determined by CCK-8 method. Interleukin-6 (IL-6) expression was investigated by real-time PCR after U937 cells were treated with nicotine, P.g-LPS and their combination. In human umbilical vein endothelial cells (HUVECs), the expressions of monocyte chemoattractant protein CCL-8 and adhesion molecules including vascular cell adhesion molecule 1 (Vcam-1), very late antigen 4 alpha (VLA4α), tumor necrosis factor receptor superfamily member 4 (OX40) and OX40 ligand (OX40L) were detected by real-time PCR or Western blotting assays after HUVEC cells were treated with nicotine, P...
October 18, 2015: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Min Cho, Jinjong Myoung
Kaposi’s sarcoma-associated herpesvirus (KSHV) belongs to the human gammaherpesvirus subfamily and is associated with malignancies of endothelial origin (Kaposi’s sarcoma, KS) and B-cell origin [primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD)]. Viral lytic replication is known to be required for KS and MCD. As KSHV-related tumours mostly develop in human subjects when the immune system is compromised by immunosuppressive regimen, human immunodeficiency virus infection or some genetic deficiencies, KSHV-specific immune responses are believed to be important in the control of KSHV replication...
December 2015: Journal of General Virology
Qiaozhen Wu, Ying Tang, Xiaoyun Hu, Qin Wang, Wei Lei, Linfu Zhou, Jianan Huang
BACKGROUND AND OBJECTIVE: Glycyrrhizic acid (GA) has been reported to have attenuating airway inflammation effects in asthma mouse model. However, the potential molecular mechanisms by which GA exerts anti-inflammatory effects on ovalbumin (OVA)-induced allergic asthma have not been well elaborated. METHODS: The effect of GA on OVA-sensitized and challenged mice was investigated. The effect of GA on anti-OX40 mAb stimulated splenocytes from asthma mice model was also examined...
January 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
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