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CD40 Ligand

Yue Li, Yunyan Wei, Weiwei Yuan, Qiqing Huang, Yaya Zhao, Weihong Zhao, Wei Xu, Jianqing Wu
The ligand of CD40, known as CD154 or CD40L, is the key to immunostimulatory and anticancer activity, but how CD40L affects cellular senescence is unclear. Thus, we studied a membrane‑stable mutant form CD40L (CD40L‑M) to explore tumor growth and cellular senescence in CD40‑positive NSCLC cells. We found that CD40L‑M‑expressing cells had senescent characteristics, including reduced cell proliferation and enlargement, increased SA‑β‑gal staining activity, and overexpression of several cell cycle regulators p53 and p21...
May 2018: Oncology Reports
Sallu Jabati, Jawed Fareed, Jeffrey Liles, Abigail Otto, Debra Hoppensteadt, Jack Bontekoe, Trung Phan, Amanda Walborn, Mushabbar Syed
The purpose of this study was to determine whether there are any differences in the levels of inflammatory, thrombotic, and collagen turnover biomarkers between individuals with atrial fibrillation (AF) and healthy volunteers. Circulating plasma levels of plasminogen activator inhibitor 1 (PAI-1), CD40-ligand (CD40-L), nucleosomes (which are indicators of cell death), C-reactive protein (CRP), procollagen III N-terminal propeptide (PIIINP), procollagen III C-terminal propeptide (PIIICP), procollagen I N-terminal propeptide, tissue plasminogen activator, and von Willebrand factor were analyzed as potential biomarkers of AF...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
Katarina Stanko, Christina Iwert, Christine Appelt, Katrin Vogt, Julia Schumann, Franziska Janina Strunk, Stefanie Ahrlich, Stephan Schlickeiser, Chiara Romagnani, Karsten Jürchott, Christian Meisel, Gerald Willimsky, Anja A Kühl, Birgit Sawitzki
Recent findings demonstrated proinflammatory functions of interleukin (IL)-9-producing T helper type (Th) 9 cells in the pathogenesis of intestinal bowel diseases (IBDs). However, also antiinflammatory properties have been ascribed to Th9 cells, pointing to a functional heterogeneity. To dissect the specific expression pattern and, especially, diversity of murine antigen-specific Th9 cells, we applied single cell transcription profiling. Th9 cells displayed reduced expression of typical activation markers, such as Cd40 ligand and Cd96 , whereas expression of Cd25 and Cd83 was increased compared with other Th subsets...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
S Støy, V C Patel, J P Sturgeon, G K Manakkat Vijay, T Lisman, W Bernal, D L Shawcross
BACKGROUND: Thrombocytopenia and circulating dysfunctional immune cells are commonly observed in patients with cirrhosis. Platelets may form complexes with neutrophils, monocytes and T cells modulating their function. We recently reported increased frequencies of platelet-complexed neutrophils in cirrhosis with evidence of neutrophil activation upon contact with healthy platelets in vitro. Whether this occurs in vivo following platelet transfusion and contributes to systemic inflammation and endothelial activation is unknown...
March 12, 2018: Alimentary Pharmacology & Therapeutics
Susanne Roser-Page, Tatyana Vikulina, Kanglun Yu, Meghan E McGee-Lawrence, M Neale Weitzmann
Objective: Immunosuppressive biologics are used in the management of RA and additional immunomodulators are under investigation including modulators of the CD40/CD40 ligand (CD40L) costimulation pathway. Tampering with immune function can have unanticipated skeletal consequences due to disruption of the immuno-skeletal interface, a nexus of shared cells and cytokine effectors serving discrete functions in both immune and skeletal systems. In this study, we examined the effect of MR1, a CD40L neutralizing antibody, on physiological bone remodelling in healthy mice...
March 7, 2018: Rheumatology
Shinya Yamamoto, Kazuhiko Matsuo, Daisuke Nagakubo, Shintaro Higashiyama, Keiji Nishiwaki, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama
CCR4 is a major chemokine receptor expressed by Treg cells that downregulate immune responses. Here, we investigated the role of CCR4-mediated Treg cell recruitment in antigen-specific immune responses. CCR4-deficient mice immunized intramuscularly with ovalbumin (OVA) showed enhanced OVA-specific IgG responses. Furthermore, intramuscular administration of OVA induced the expression of MDC/CCL22, a ligand for CCR4, in macrophages of the muscle tissues, and enhanced the recruitment of CCR4+ Treg cells in wild-type mice, whereas this recruitment of Treg cells was severely impaired in CCR4-deficient mice...
February 8, 2018: Journal of Pharmacological Sciences
Otavio Cabral-Marques, Tabata Takahashi França, Ashraf Al-Sbiei, Lena Friederike Schimke, Taj Ali Khan, Claudia Feriotti, Tania Alves da Costa, Osvaldo Reis Junior, Cristina Worm Weber, Janaíra Fernandes Ferreira, Fabiola Scancetti Tavares, Claudia Valente, Regina Sumiko Watanabe Di Gesu, Asif Iqbal, Gabriela Riemekasten, Gustavo Pessini Amarante-Mendes, José Alexandre Marzagão Barbuto, Beatriz Tavares Costa-Carvalho, Paulo Vitor Soeiro Pereira, Maria J Fernandez-Cabezudo, Vera Lucia Garcia Calich, Luigi D Notarangelo, Troy R Torgerson, Basel K Al-Ramadi, Hans D Ochs, Antonio Condino-Neto
BACKGROUND: Patients with X-linked Hyper-IgM syndrome (X-HIGM) due to CD40 ligand (CD40L) deficiency often present episodic, cyclic or chronic neutropenia, suggesting abnormal neutrophil development in the absence of CD40L-CD40 interaction. However, even when not neutropenic and despite immunoglobulin (Ig) replacement therapy, CD40L-deficient patients are susceptible to life-threatening infections caused by opportunistic pathogens, suggesting impaired function of phagocytes and the need of novel therapeutic approaches...
March 5, 2018: Journal of Allergy and Clinical Immunology
Lu Han, Lu Dai, Yuan-Fei Zhao, Hai-Yang Li, Ou Liu, Feng Lan, Wen-Jian Jiang, Hong-Jia Zhang
Acute aortic dissection is one of the most lethal cardiovascular disease. The major histopathological feature of AAD is medial degradation, especially breakdown of elastin and collagen. However, the underlying mechanism remains a mystery. Platelets expressed CD40 Ligand (CD40L) is recently recognised as a key effector of cardiovascular disease development through its pro-inflammatory effect. To clarify the role of CD40L in AAD, we examined level of CD40L in human blood serum samples and found that it is significantly higher in AAD patients compared with healthy subjects (26...
March 4, 2018: Aging
Paweł P Wołkow, Anna Gębska, Ryszard Korbut
Dendritic cells (DCs) play a crucial role in the development of adaptive immune response. Monocyte-derived dendritic cells (MDDCs) are generated in vitro to study DC biology and for use in immunotherapy. However, procedures to generate MDDCs vary and an impact this may have on their final phenotype is insufficiently studied. Monocytes isolated from healthy blood donors were cultured for 7 days with granulocyte-macrophage colony stimulating factor (50 ng/mL) and low (500 IU/mL, L-IL4) or high (1000 IU/mL, H-IL4) interleukin 4 (IL4), to obtain immature DCs and for the following 2 days with addition of soluble CD40 ligand (500 ng/mL) and prostaglandin E2 (1 μg/mL) to obtain mature DCs...
February 28, 2018: International Immunopharmacology
Shiferaw Jenberie, Hanna L Thim, J Oriol Sunyer, Karsten Skjødt, Ingvill Jensen, Jorunn B Jørgensen
While TLR-activated pathways are key regulators of B cell responses in mammals, their impact on teleost B cells are scarcely addressed. Here, the potential of Atlantic salmon B cells to respond to TLR ligands was shown by demonstrating a constitutive expression of nucleic-acid sensing TLRs in magnetic sorted IgM+ cells. Of the two receptors recognizing CpG in teleosts, tlr9 was the dominating receptor with over ten-fold higher expression than tlr21. Upon CpG-stimulation, IgM secretion increased for head kidney (HK) and splenic IgM+ cells, while blood B cells were marginally affected...
February 23, 2018: Scientific Reports
Т Zaikina, V Babadjan, N Ryndina, O Borzova, Yu Kovalyova
Aim of study‒ estimate the influence of the metformin therapy on the sCD40-ligand and sVE-cadherinlevels among patients with acute myocardial infarction and concomitant type 2 diabetes mellitus. The study included44patients with AMI and type 2 diabetes whichweredividedintotwo groupsdependingonthe glucose lowering drugs they have been taken: I group ‒ 21patients who have been taken metformin; II group ‒ 23patients, who have been taken short-acting insulin. Accordingtotheobtainedresults using of metformin as a glucose lowering drug in comparison with patients who have been taken short-acting insulin causes faster decreasing of the sCD40L level (-29,3% and -24,4% accordingly; р<0,05)...
January 2018: Georgian Medical News
Elena Y Senchenkova, Janice Russell, Shantel A Vital, Alper Yildirim, A Wayne Orr, D Neil Granger, Felicity N E Gavins
Angiotensin II (Ang-II)-induced hypertension is associated with accelerated thrombus formation in arterioles and leukocyte recruitment in venules. The mechanisms that underlie the prothrombotic and proinflammatory responses to chronic Ang-II administration remain poorly understood. We evaluated the role of CD40/CD40 ligand (CD40L) signaling in Ang-II-mediated microvascular responses and assessed whether and how soluble CD40L (sCD40L) contributes to this response. Intravital video microscopy was performed to analyze leukocyte recruitment and dihydrorhodamine-123 oxidation in postcapillary venules...
February 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Robert Wilson, Mateusz Makuch, Anne-Kathrin Kienzler, James Varley, Jennifer Taylor, Mark Woodhall, Jacqueline Palace, M Isabel Leite, Patrick Waters, Sarosh R Irani
Autoantibodies to aquaporin-4 (AQP4) are pathogenic in neuromyelitis optica spectrum disorder (NMOSD). However, it is not known which B cells are the major contributors to circulating AQP4 antibodies nor which conditions promote their generation. Our experiments showed CD19+CD27++CD38++ circulating ex vivo antibody-secreting cells did not produce AQP4 antibodies under several culture conditions. To question whether other cells in circulation were capable of AQP4 antibody production, B cells were differentiated into antibody-secreting cells in vitro...
February 13, 2018: Brain: a Journal of Neurology
Jane A O'Halloran, Eimear Dunne, Willard Tinago, Stephanie Denieffe, Dermot Kenny, Patrick W G Mallon
OBJECTIVES: Altered platelet function has been proposed as an underlying mechanism to explain increased risk of myocardial infarction in people living with HIV associated with use of the nucleoside reverse transcriptase inhibitor abacavir (ABC). We aimed to examine changes in platelet biomarkers in people living with HIV switching from ABC. METHODS: In a prospective, 48-week substudy of virally suppressed HIV-1-positive subjects randomized to remain on ABC/lamivudine (ABC/3TC) or switch to tenofovir disoproxil fumarate/emtricitabine, we measured soluble glycoprotein VI (sGPVI), soluble P-selectin, soluble CD40 ligand and von Willebrand factor in plasma collected over time and assessed differences using mixed effect models...
February 12, 2018: AIDS
Lei Wang, Yuanming Li, Xiaojin Gong
This study was designed to assess the relationship between changes in peripheral inflammatory factors of patients complicated with non-alcoholic fatty liver disease (NAFLD) undergoing coronary artery bypass grafting (CABG) before and after operation, and their prognosis. A total of 68 patients with stable angina pectoris treated in Xinjiang Hospital who underwent CABG at some point between August of 2013 and August of 2015 were enrolled in the study, and divided into the NAFLD group (n=31) and the non-NAFLD group (n=37) according to the presence of the condition or its absence...
January 2018: Experimental and Therapeutic Medicine
Isaac R Melamed, Melinda Heffron, Alessandro Testori, Kellie Lipe
Research has shown that a subset of the autism spectrum disorder (ASD) population presents with immune dysregulation. To explore this topic further, we investigated the efficacy and tolerability of intravenous immunoglobulin (IVIG) infusion in children with ASD. In this study, participants were recruited based on a diagnosis of autistic disorder, Asperger's disorder, or pervasive developmental disorder not otherwise specified. Participants also showed evidence of immune dysfunction based on abnormal levels of specific biomarkers, including CD40 ligand (CD154), lymphocyte stimulation, and T or B cell dysfunction...
February 10, 2018: Autism Research: Official Journal of the International Society for Autism Research
Fanyou Ning, Chong Wang, Suling Niu, Haiyan Xu, Kai Xia, Nan Wang
The Polycomb Repressive Complex 2 (PRC2) component PHD Finger Protein 19 ( phf19 ) gene has been identified to be associated with rheumatoid arthritis (RA) risk. Here we show that Phf19 is highly expressed in murine germinal centers (GCs) and RA patients. To investigate the function of Phf19 in lymphocytes, we generated RAG1-deficient mice reconstituted with Phf19 or control-vector transduced bone marrow (BM) cells. Lymphogenesis in primary lymphoid tissues of Phf19-RM is normal, however, Phf19-RM form enlarged GCs and generate more antibody-secreting cells (ASCs)...
2018: American Journal of Translational Research
Irene Soleto, Uwe Fischer, Carolina Tafalla, Aitor G Granja
Dendritic cells (DCs) are highly specialized antigen-presenting cells that bridge innate and adaptive immune responses in vertebrates, being key modulators in the initiation of specific responses. Although teleost fish present the main elements of a fully developed adaptive immune system, not many studies have focused on identifying specific DC subsets in teleost species. Previous work from our group identified in rainbow trout (Oncorhynchus mykiss) skin a DC subpopulation co-expressing CD8α and major histocompatibility complex II β on the cell surface...
2018: Frontiers in Immunology
Sara W Feigelson, Adam Solomon, Adi Biram, Miki Hatzav, Moria Lichtenstein, Ofer Regev, Stav Kozlovski, Diana Varol, Caterina Curato, Dena Leshkowitz, Steffen Jung, Ziv Shulman, Ronen Alon
Protective immune responses depend on the formation of immune synapses between T cells and antigen-presenting cells (APCs). The two main LFA-1 ligands, ICAM-1 and ICAM-2, are co-expressed on many cell types, including APCs and blood vessels. Although these molecules were suggested to be key players in immune synapses studied in vitro, their contribution to helper T cell priming in vivo is unclear. Here, we used transgenic mice and intravital imaging to examine the role of dendritic cell (DC) ICAM-1 and ICAM-2 in naive CD4 T cell priming and differentiation in skin-draining lymph nodes...
January 23, 2018: Cell Reports
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