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CD40 Ligand

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https://www.readbyqxmd.com/read/29352038/microenvironment-induced-cd44v6-promotes-early-disease-progression-in-chronic-lymphocytic-leukemia
#1
Julia C Gutjahr, Eva Szenes, Lisa Tschech, Daniela Asslaber, Michaela Schlederer, Simone Roos, Xiaobing Yu, Tamara Girbl, Christina Sternberg, Alexander Egle, Fritz Aberger, Ronen Alon, Lukas Kenner, Richard Greil, Veronique Orian-Rousseau, Tanja N Hartmann
Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the microenvironment. We have previously found that in vitro reconstitution of this microenvironment induces specific variant isoforms of the adhesion molecule CD44, which confer human CLL with high affinity to hyaluronan (HA). Here, we determined the in vivo contribution of standard CD44 and its variants to leukemic B-cell homing and proliferation in Tcl1 transgenic mice with a B-cell-specific CD44 deficiency. In these mice, leukemia onset was delayed and leukemic infiltration of spleen, liver, and lungs, but not of bone marrow was decreased...
January 19, 2018: Blood
https://www.readbyqxmd.com/read/29348660/generation-and-characterization-of-alloantigen-specific-regulatory-t-cells-for-clinical-transplant-tolerance
#2
James M Mathew, Jessica H Voss, Scott T McEwen, Iwona Konieczna, Arjun Chakraborty, Xuemei Huang, Jie He, Lorenzo Gallon, Richard S Kornbluth, Joseph R Leventhal
Donor-specific CD4+CD127-CD25+FOXP3+ regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel expansion protocol to stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B cells that expressed mature antigen-presenting cell markers. This avoided the use of CD40L-expressing stimulator cells that might otherwise result in potential cellular contamination. Purified allogeneic "recipient" CD4+CD25+ Tregs were stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2, TGFβ and sirolimus (SRL)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29346441/a-portable-system-for-processing-donated-whole-blood-into-high-quality-components-without-centrifugation
#3
Sean C Gifford, Briony C Strachan, Hui Xia, Eszter Vörös, Kian Torabian, Taylor A Tomasino, Gary D Griffin, Benjamin Lichtiger, Fleur M Aung, Sergey S Shevkoplyas
BACKGROUND: The use of centrifugation-based approaches for processing donated blood into components is routine in the industrialized world, as disparate storage conditions require the rapid separation of 'whole blood' into distinct red blood cell (RBC), platelet, and plasma products. However, the logistical complications and potential cellular damage associated with centrifugation/apheresis manufacturing of blood products are well documented. The objective of this study was to evaluate a proof-of-concept system for whole blood processing, which does not employ electromechanical parts, is easily portable, and can be operated immediately after donation with minimal human labor...
2018: PloS One
https://www.readbyqxmd.com/read/29345851/the-immunosuppressive-effects-of-cd4-cd25-regulatory-t-cells-on-dendritic-cells-in-patients-with-chronic-hepatitis-b
#4
Pei-Pei Zhou, Juan Xu, Ming-Jia Dai, Yin-Yue Shi, Gui-Ping Wu, Yuan Fang, Xue-Bing Yan
The characteristics and functions of CD4+ CD25+ regulatory T cells (Tregs) have been well defined in murine and human systems. However, the interaction or cross-talk between CD4+ CD25+ Tregs and dendritic cells (DCs) remains controversial. In this study, the effects of chronic hepatitis B (CHB) CD4+ CD25+ Tregs on the maturation and function of monocyte-derived DCs were examined. The results showed that CD4+ CD25+ render the DCs inefficient as antigen-presenting cells (APCs) despite prestimulation with CD40 ligand...
January 18, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29342141/monitoring-t-cell-dendritic-cell-interactions-in-vivo-by-intercellular-enzymatic-labelling
#5
Giulia Pasqual, Aleksey Chudnovskiy, Jeroen M J Tas, Marianna Agudelo, Lawrence D Schweitzer, Ang Cui, Nir Hacohen, Gabriel D Victora
Interactions between different cell types are essential for multiple biological processes, including immunity, embryonic development and neuronal signalling. Although the dynamics of cell-cell interactions can be monitored in vivo by intravital microscopy, this approach does not provide any information on the receptors and ligands involved or enable the isolation of interacting cells for downstream analysis. Here we describe a complementary approach that uses bacterial sortase A-mediated cell labelling across synapses of immune cells to identify receptor-ligand interactions between cells in living mice, by generating a signal that can subsequently be detected ex vivo by flow cytometry...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29329699/soluble-cd40-ligand-disrupts-the-blood-brain-barrier-and-exacerbates-inflammation-in-experimental-autoimmune-encephalomyelitis
#6
Hiroki Masuda, Masahiro Mori, Kenta Umehara, Tomomi Furihata, Tomohiko Uchida, Akiyuki Uzawa, Satoshi Kuwabara
Serum soluble CD40 ligand (sCD40L) has been reported to positively correlate with the albumin quotient, a marker of blood-brain barrier (BBB) breakdown, in patients with multiple sclerosis (MS). To clarify the mechanisms of sCD40L in MS pathophysiology, sCD40L was administered to experimental autoimmune encephalomyelitis (EAE) mice and a human brain microvascular endothelial cell (HBMEC)-based BBB model. The high-dose sCD40L group showed a worse EAE score than the low-dose and control groups. BBB permeability was increased by administering sCD40L in a HBMEC-based BBB model...
January 3, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29306404/cerebrospinal-fluid-pentraxin-3-and-cd40-ligand-in-anti-n-menthyl-d-aspartate-receptor-encephalitis
#7
Baozhu Liu, Peiying Ai, Dong Zheng, Ying Jiang, Xiaojia Liu, Suyue Pan, Honghao Wang
Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system whose pathogenesis involves interleukin (IL)-6 and IL-17A. We examined the correlations between CSF concentrations of the acute-phase protein pentraxin 3 (PTX3), the chronic inflammatory mediator CD40L, IL-6, and IL-17A in anti-NMDAR encephalitis, and the impact on clinical outcome. PTX3, CD40L, IL-6, and IL-17A were significantly higher in the CSF of patients with anti-NMDAR encephalitis than in controls...
February 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29303623/x-linked-hyper-igm-syndrome-a-phenotype-of-crohn-s-disease-with-hemophagocyticlymphohistiocytosis
#8
Kun-Yin Qiu, Xiong-Yu Liao, Ruo-Hao Wu, Ke Huang, Jian-Pei Fang, Dun-Hua Zhou
X-linked hyper-immunoglobulin M (IgM) syndrome is characterized by recurrent infections, low or undetectable levels of IgG and IgA, and normal to increased serum IgM, and is also rare. It is associated with mutation in the gene encoding CD40 ligand. This study aimed to describe the first international report of hemizygous CD40LG c.542G>A mutation in a 5-year-old boy with a phenotype of Crohn's disease and hemophagocyticlymphohistiocytosis. Also, the clinical implications of this mutation and associated atypical phenotype are discussed...
January 5, 2018: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29249591/relationship-between-cardiac-troponin-and-thrombo-inflammatory-molecules-in-prediction-of-outcome-after-acute-ischemic-stroke
#9
Peter Csecsei, Gabriella Pusch, Erzsebet Ezer, Timea Berki, Laszlo Szapary, Zsolt Illes, Tihamer Molnar
BACKGROUND: In patients with acute ischemic stroke (AIS) without cardiovascular complications, we investigated the association of serum concentration of cardiac troponin (high-sensitivity cardiac troponin T [hs-cTnT]) with thrombo-inflammatory markers. METHODS: Thirty-five patients with first-ever AIS were prospectively examined. Serum hs-cTnT was measured 6 and 24 hours after stroke, whereas S100B, high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand, tissue plasminogen activator (tPA), monocyte chemoattractant protein-1 (MCP-1), and P-selectin were measured 6 and 72 hours after stroke...
December 14, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29245066/immuno-biological-comparison-of-hepatic-stellate-cells-in-a-reverted-and-activated-state
#10
Mehdi Najar, Hussein Fayyad-Kazan, Wissam H Faour, Adil El Taghdouini, Gordana Raicevic, Leo A van Grunsven, Mustapha Najimi, Etienne Sokal, Laurence Lagneaux
Human hepatic stellate cells (HSCs) demonstrated great immunological plasticity with important consequences for liver cell therapy. Activated HSCs (aHSCs) are in vitro reverted (rHSCs) to a quiescent-like phenotype with potential benefit to reduce liver fibrosis. The goal of this study is to establish and compare the immunological profile of activated and in vitro reverted HSCs and to investigate the impact of inflammatory priming on the immunobiology of both HSCs populations. The distribution of inflammatory primed activated and reverted HSCs across the different phases of the cell cycle is assessed by flow cytometry...
December 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29234038/sodium-tanshinone-iia-sulfate-adjunct-therapy-reduces-high-sensitivity-c-reactive-protein-level-in-coronary-artery-disease-patients-a-randomized-controlled-trial
#11
Siming Li, Yang Jiao, Hanjay Wang, Qinghua Shang, Fang Lu, Li Huang, Jiangang Liu, Hao Xu, Keji Chen
High-sensitivity C-reactive protein (hs-CRP) is independently associated with cardiovascular events in coronary artery disease (CAD) patients and reducing the hs-CRP level may further benefit this population. We conduct this parallel design, randomized-controlled trial to assess the effectiveness of adjunct sodium tanshinone IIA sulfate (STS) therapy on circulating inflammation markers in CAD patients. Unstable angina or non-ST-elevation myocardial infarction patients with increased hs-CRP level were randomly assigned to atorvastatin-based standard medical therapy or standard therapy plus STS injection (80 mg, once daily for 14 consecutive days)...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222897/platelet-related-cytokines-among-normal-body-mass-index-overweight-and-obese-malaysians
#12
Nasrin Riyahi, Eusni Rahayu Mohd Tohit, Subashini C Thambiah, Zuriati Ibrahim
BACKGROUND AND OBJECTIVES: Recent studies have reported that obesity is associated with platelet activation and systemic inflammation. Malaysia has the highest prevalence of obesity, hence, this research is performed to evaluate the development of low-grade inflammation and platelet activation, measured using soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-sel), and to determine their association with obesity. In addition, we assessed the mean platelet volume (MPV) and platelet count (PLT), which are novel parameters consistently associated with obesity...
2018: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29215030/traf3-negatively-regulates-platelet-activation-and-thrombosis
#13
Rui Zhang, Guoying Zhang, Binggang Xiang, Xiaofeng Chen, Lijang Tang, Shaojun Shi, Yani Liu, Xun Ai, Ping Xie, Zhenyu Li
CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29205315/repository-corticotropin-injection-exerts-direct-acute-effects-on-human-b-cell-gene-expression-distinct-from-the-actions-of-glucocorticoids
#14
Ann L Benko, Carl A McAloose, Patrice M Becker, Dale Wright, Teresa Sunyer, Yuka Imamura Kawasawa, Nancy J Olsen, William J Kovacs
Repository corticotropin injection (RCI, H.P Acthar® Gel) has been approved for use in the management of multiple autoimmune and inflammatory diseases for over a half-century, but its mechanism of action is not well understood. We used RNA -Seq methods to define RCI-regulated mRNAs in cultured human B cells under conditions of activation by IL4 and CD40 ligand. Following IL4/CD40L activation and RCI treatment we found up-regulation of 115 unique mRNA transcripts and downregulation of 80 unique mRNAs. The effect on these RNA levels was dose-dependent for RCI and was distinct from changes in mRNA expression induced by treatment with a potent synthetic glucocorticoid...
December 4, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29194956/at-the-mercy-of-platelet-primers
#15
Judith M E M Cosemans
In this issue of the Journal of Thrombosis and Haemostasis, Branchford et al. [1] present novel data on the role of Mer tyrosine kinase in platelet function and thrombosis. Mer forms, together with Axl and Tyro3, the TAM receptor family of Growth arrest-specific (Gas6) receptors. The vitamin-K dependent protein Gas6 is regarded as a platelet primer, next to other molecules such as epinephrin, insulin-like growth factor-1 and 2, matrix metalloproteinase-1 and 2, oxided low-density lipoprotein, prostaglandin E2, soluble CD40 ligand and thrombopoeitin [2]...
December 1, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29194343/blood-mixing-upregulates-platelet-membrane-bound-cd40-ligand-expression-in-vitro-independent-of-abo-compatibility
#16
Go-Shine Huang, Mei-Hua Hu, Tso-Chou Lin, Yi-Chang Lin, Yi-Ting Tsai, Chih-Yuan Lin, Hung-Yen Ke, Xu-Zhi Zheng, Chien-Sung Tsai
Platelets play a central role in the inflammation response via CD40 ligand (CD40L) expression, which may lead to transfusion reactions. The precise role of platelet CD40L-mediated inflammation in transfusion reactions is unclear. Therefore, we assessed the effects of in vitro blood mixing on platelet CD40L expression. In addition, we examined the effect of ABO compatibility on CD40L expression. Donor packed red blood cells were acquired from a blood bank, and recipient blood was obtained from patients undergoing cardiac surgery and prepared as washed platelets...
November 30, 2017: Shock
https://www.readbyqxmd.com/read/29162926/the-relationship-between-soluble-cd40-ligand-level-and-atherosclerosis-in-white-coat-hypertension
#17
Yu-Qing Huang, L I Jie, Ji-Yan Chen, Song-Tao Tang, Cheng Huang, Ying-Qing Feng
This study was designed to examine the distribution of plasma soluble CD40 ligand (sCD40L), and its relationship with carotid intima-media thickness (CIMT) in healthy controls and subjects with white-coat hypertension (WCH) or hypertension (HT). Thirty-five patients with HT, 35 patients with WCH, and 35 healthy controls were enrolled. The normal group (CIMT < 0.9 mm), subclinical atherosclerosis group (0.9 mm ≤ CIMT < 1.2 mm) and atherosclerosis group (CIMT ≥ 1.2 mm) were grouped based on the value of CIMT...
November 21, 2017: Journal of Human Hypertension
https://www.readbyqxmd.com/read/29155846/soluble-cd40-ligand-directly-alters-glomerular-permeability-and-may-act-as-a-circulating-permeability-factor-in-fsgs
#18
Sophie Doublier, Cristina Zennaro, Luca Musante, Tiziana Spatola, Giovanni Candiano, Maurizio Bruschi, Luca Besso, Massimo Cedrino, Michele Carraro, Gian Marco Ghiggeri, Giovanni Camussi, Enrico Lupia
CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli...
2017: PloS One
https://www.readbyqxmd.com/read/29129918/intratumoral-cd40-activation-and-checkpoint-blockade-induces-t-cell-mediated-eradication-of-melanoma-in-the-brain
#19
Manisha Singh, Christina Vianden, Mark J Cantwell, Zhimin Dai, Zhilan Xiao, Meenu Sharma, Hiep Khong, Ashvin R Jaiswal, Faisal Faak, Yared Hailemichael, L M E Janssen, Uddalak Bharadwaj, Michael A Curran, Adi Diab, Roland L Bassett, David J Tweardy, Patrick Hwu, Willem W Overwijk
CD40 agonists bind the CD40 molecule on antigen-presenting cells and activate them to prime tumor-specific CD8+ T cell responses. Here, we study the antitumor activity and mechanism of action of a nonreplicating adenovirus encoding a chimeric, membrane-bound CD40 ligand (ISF35). Intratumoral administration of ISF35 in subcutaneous B16 melanomas generates tumor-specific, CD8+ T cells that express PD-1 and suppress tumor growth. Combination therapy of ISF35 with systemic anti-PD-1 generates greater antitumor activity than each respective monotherapy...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29127283/environmental-sensing-by-mature-b-cells-is-controlled-by-the-transcription-factors-pu-1-and-spib
#20
Simon N Willis, Julie Tellier, Yang Liao, Stephanie Trezise, Amanda Light, Kristy O'Donnell, Lee Ann Garrett-Sinha, Wei Shi, David M Tarlinton, Stephen L Nutt
Humoral immunity requires B cells to respond to multiple stimuli, including antigen, membrane and soluble ligands, and microbial products. Ets family transcription factors regulate many aspects of haematopoiesis, although their functions in humoral immunity are difficult to decipher as a result of redundancy between the family members. Here we show that mice lacking both PU.1 and SpiB in mature B cells do not generate germinal centers and high-affinity antibody after protein immunization. PU.1 and SpiB double-deficient B cells have a survival defect after engagement of CD40 or Toll-like receptors (TLR), despite paradoxically enhanced plasma cell differentiation...
November 10, 2017: Nature Communications
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