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https://www.readbyqxmd.com/read/28636654/characterization-of-human-fcrl4-positive-b-cells
#1
Michel Jourdan, Nicolas Robert, Maïlys Cren, Coraline Thibaut, Christophe Duperray, Alboukadel Kassambara, Michel Cogné, Karin Tarte, Bernard Klein, Jérôme Moreaux
FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, FCRL4 is specifically expressed by memory B cells (MBCs) localized in sub-epithelial regions of lymphoid tissues. Expansion of FCRL4+ B cells has been observed in blood and other tissues in various infectious and autoimmune disorders. Currently, the mechanisms involved in pathological FCRL4+ B cell generation are actively studied, but they remain elusive. As in vivo FCRL4+ cells are difficult to access and to isolate, here we developed a culture system to generate in vitro FCRL4+ B cells from purified MBCs upon stimulation with soluble CD40 ligand and/or CpG DNA to mimic T-cell dependent and/or T-cell independent activation, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#2
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634588/antitumor-effect-of-kml-b-treated-dendritic-cells-via-induction-of-lymphocyte-activation
#3
Jong-Jin Kim, Yun-Ho Hwang, Kyung-Yun Kang, Sung-Ju Lee, Jong-Bae Kim, Jina Choi, Sung-Tae Yee
Lectins are carbohydrate-binding proteins with various biological activities, such as antitumor and immunomodulatory effects. Although lectins have various biological activities, they are still limited by cytotoxicity in normal cells. To overcome this problem, we used the noncytotoxic part of Korean mistletoe lectin B-chain (KML-B) to induce maturation of dendritic cells (DCs). A previous study reported that KML-B induces DC maturation by triggering TLR-4, including expression of costimulatory molecules (CD40, CD80, and CD86), MHC II, and secretion of cytokines in DCs...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28634479/whole-blood-profiling-of-bacillus-calmette-gu%C3%A3-rin-induced-trained-innate-immunity-in-infants-identifies-epidermal-growth-factor-il-6-platelet-derived-growth-factor-ab-bb-and-natural-killer-cell-activation
#4
Steven G Smith, Johanneke Kleinnijenhuis, Mihai G Netea, Hazel M Dockrell
Vaccination of infants with bacillus Calmette-Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28628013/modulation-of-antitumor-immune-response-in-mouse-prostate-cancer-model
#5
N Mitskevich, T Tsertsvadze, K Mchedlishvili, K Matchavariani, G Guruli
Aim of study - prostate cancer is second most common cancer in men worldwide, and fifth leading cause of death from cancer in men (6.6% of the total men deaths). Unfortunately, once cancer spreads outside of prostate, it becomes incurable. Androgen deprivation can provide some relief, but resistance will develop eventually, and at that time no effective treatment options are left to the patient. Therefore, the search of alternative treatment modalities is paramount. In this article we evaluated the role of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator - Lenalidomide and their possible impact on the immune response in the murine prostate cancer model...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28624612/human-mast-cells-present-antigen-to-autologous-cd4-t-cells
#6
Sahar Lotfi-Emran, Brant R Ward, Quang T Le, Andrea L Pozez, Masoud H Manjili, Judith Woodfolk, Lawrence B Schwartz
BACKGROUND: Mast cells (MCs), the primary effector cell of the atopic response, participate in immune defense at host/environment interfaces, yet the mechanisms by which they interact with CD4(+)-T cells has been controversial. OBJECTIVE: We utilize in situ-matured primary human MCs and matched CD4(+)-T cells to diligently assess the ability of MCs to act as antigen-presenting cells. METHODS: We examined mature human skin-derived MCs by flow cytometry for expression of antigen-presenting molecules; for their ability to stimulate CD4(+)-T cells to express CD25 and proliferate when exposed to superantigen or to CMV antigen using matched T cells and MCs from CMV seropositive or seronegative donors; and for uptake of antigens...
June 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28621946/the-acute-effects-of-fine-particulate-matter-constituents-on-blood-inflammation-and-coagulation
#7
Cong Liu, Jing Cai, Renjie Chen, Liping Qiao, Hongli Wang, Wenxi Xu, Huichu Li, Zhuohui Zhao, Haidong Kan
Limited evidence is available on the effects of various fine particulate matter (PM2.5) constituents on blood inflammation and coagulation. We examined the associations between 10 constituents and 10 circulating biomarkers in a panel of 28 urban residents with 4 repeated measurements in Shanghai, China. Based on the linear mixed-effect models, we fitted the single-constituent models, the constituent-PM2.5 joint models, and the constituent-residual models to evaluate the associations between PM2.5 constituents and 8 inflammatory biomarkers (fibrinogen, C-reactive protein, monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-1b, intercellular adhesion molecule-1, P-selectin, vascular cell adhesion molecule-1) and 2 coagulation biomarkers (plasminogen activator inhibitor-1 and soluble CD40 ligand)...
June 16, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28621565/light-emitting-diode-at-460%C3%A2-%C3%A2-%C3%A2-20%C3%A2-nm-increases-the-production-of-il-12-and-il-6-in-murine-dendritic-cells
#8
Tamires Marielem Carvalho-Costa, Maria Tays Mendes, Marcos Vinicius da Silva, Virmondes Rodrigues, Giuliana Cristina Marre Bruschi Thedei, Carlo Jose Freire Oliveira, Geraldo Thedei
BACKGROUND DATA: Light emitting diode (LED) therapy has been proposed as an option for the treatment of many skin inflammatory processes. Dendritic cells (DCs) are important cells of skin that participate in the initiation and activation of skin immunity. The modulation of these cells by LED could explain much of its effects. OBJECTIVE: Thus, the aim of this study was to examine the effects of LED at 460 ± 20 nm on cytokine production and the expression of surface markers on DCs...
June 15, 2017: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/28620145/hepatic-stroma-educated-regulatory-dcs-suppress-cd8-t-cell-proliferation-in-mice
#9
Qian Wang, Hao He, Dongwei Chen, Chao Wang, Yingping Xu, Wengang Song
Liver dendritic cells (DCs) display immunosuppressive activities and inhibit the CD4+ T cell response. The present study assessed whether and how liver DCs suppress CD8+ T cells. We found that bone marrow-derived mature DCs incubated with liver stromal cells were characterized by a longer life span, reduced CD11c, IA/IE, CD80, CD86, and CD40 expression, and increased CD11b expression. These unique liver stromal cell-educated mature DCs (LSed-DCs) stimulated CD8+ T cells to express CD25 and CD69, but inhibited their proliferation...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28619427/soluble-cd40-ligand-derived-from-serum-is-not-correlated-with-early-ms
#10
Hamid Zahednasab, Bahaadin Siroos, Mohammad Balood, Mohammad Sajad Emami Aleagha, Mohammad Hossein Harirchian
BACKGROUND: Soluble CD40 ligand (sCD154) is a proinflammatory and prothrombotic ligand belonging to the tumor necrosis factor family. It has been shown by a variety of studies that sCD154 is elevated in the serum of patients afflicted with system autoimmune diseases. The aim of our study was to address whether sCD154 is increased in disease affected by Multiple Sclerosis (MS). METHODS: Twenty MS patients who have been newly diagnosed as clinically definite multiple sclerosis (CDMS) along with twenty age and sex matched healthy individuals were recruited for this study...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28619093/serial-immunomonitoring-of-cancer-patients-receiving-combined-antagonistic-anti-cd40-and-chemotherapy-reveals-consistent-and-cyclical-modulation-of-t-cell-and-dendritic-cell-parameters
#11
Alison M McDonnell, Alistair Cook, Bruce W S Robinson, Richard A Lake, Anna K Nowak
BACKGROUND: CD40 signalling can synergise with chemotherapy in preclinical cancer models, and early clinical studies are promising. We set out to define the immunological changes associated with this therapeutic combination to identify biomarkers for a response to the therapy. Here, we present serial immunomonitoring examining dendritic cell and T cell subpopulations over sequential courses of chemoimmunotherapy. METHODS: Fifteen patients with mesothelioma received up to six 21-day cycles of pemetrexed plus cisplatin chemotherapy and anti-CD40 (CP-870,893)...
June 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28610909/rip1-has-a-role-in-cd40-mediated-apoptosis-in-human-follicular-lymphoma-cells
#12
Jemal Adem, Mine Eray, Jonna Eeva, Ulla Nuutinen, Jukka Pelkonen
CD40 is a cell surface receptor which belongs to tumor necrosis factor receptor (TNFR) family members. It transmits signals that regulate diverse cellular responses such as proliferation, differentiation, adhesion molecule expression and apoptosis. Unlike other TNFR family members (TRAIL-R, Fas-R and TNFR1), the CD40 cytoplasmic tail lacks death domain. However, CD40 is capable of inducing apoptosis in different types of cancer cells including lymphoma. The apoptotic effect of CD40 is linked to the involvement of Fas, TRAIL or receptor interacting protein 1 (RIP1) kinase...
June 10, 2017: Immunobiology
https://www.readbyqxmd.com/read/28609750/association-of-plasma-cd40l-with-acute-chest-syndrome-in-sickle-cell-anemia
#13
Vanessa Tonin Garrido, Laura Sonzogni, Siana Nkya Mtatiro, Fernando F Costa, Nicola Conran, Swee Lay Thein
Platelet activation and platelet-derived cytokines contribute to the vascular inflammation and increased thrombotic activity known to occur in patients with sickle cell anemia (SCA). CD40 ligand (CD40L), a platelet-associated pro-inflammatory molecule that promotes endothelial cell activation, is elevated in the circulation of SCA patients. We sought to evaluate the association of CD40L and inflammation with sickle-related clinical complications and laboratory variables in SCA patients. Soluble CD40L, thrombospondin (TSP)-1 and tumor necrosis factor (TNF)-α were determined in the platelet-poor plasma of healthy individuals and steady-state SCA patients by ELISA...
June 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28609704/sphingosine-1-phosphate-s1p-suppresses-the-collagen-induced-activation-of-human-platelets-via-s1p4-receptor
#14
Takashi Onuma, Kumiko Tanabe, Yuko Kito, Masanori Tsujimoto, Kodai Uematsu, Yukiko Enomoto, Rie Matsushima-Nishiwaki, Tomoaki Doi, Kiyoshi Nagase, Shigeru Akamatsu, Haruhiko Tokuda, Shinji Ogura, Toru Iwama, Osamu Kozawa, Hiroki Iida
Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation...
June 2, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28609584/endothelial-nitric-oxide-synthase-inhibition-triggers-inflammatory-responses-in-the-brain-of-male-rats-exposed-to-ischemia-reperfusion-injury
#15
Rosaria Greco, Chiara Demartini, Anna Maria Zanaboni, Fabio Blandini, Diana Amantea, Cristina Tassorelli
Nitric oxide (NO) derived from endothelial NO synthase (eNOS) plays a role in preserving and maintaining the brain's microcirculation, inhibiting platelet aggregation, leukocyte adhesion, and migration. Inhibition of eNOS activity results in exacerbation of neuronal injury after ischemia by triggering diverse cellular mechanisms, including inflammatory responses. To examine the relative contribution of eNOS in stroke-induced neuroinflammation, we analyzed the effects of systemic treatment with l-N-(1-iminoethyl)ornithine (L-NIO), a relatively selective eNOS inhibitor, on the expression of MiR-155-5p, a key mediator of innate immunity regulation and endothelial dysfunction, in the cortex of male rats subjected to transient middle cerebral artery occlusion (tMCAo) followed by 24 hr of reperfusion...
June 13, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28608165/platelet-related-biomarkers-and-their-response-to-inhibition-with-aspirin-and-p2y12-receptor-antagonists-in-patients-with-acute-coronary-syndrome
#16
Angela Lowenstern, Robert F Storey, Megan Neely, Jie-Lena Sun, Dominick J Angiolillo, Christopher P Cannon, Anders Himmelmann, Kurt Huber, Stefan K James, Hugo A Katus, Joao Morais, Agneta Siegbahn, Phillippe Gabriel Steg, Lars Wallentin, Richard C Becker
The PLATelet inhibition and patient Outcomes (PLATO) trial showed that treatment with ticagrelor reduced the rate of death due to vascular causes, myocardial infarction and stroke when compared to clopidogrel in patients with ST-elevation or non-ST-elevation acute coronary syndrome (ACS). While the comparative benefit of ticagrelor over clopidogrel increased over time, event rates accrued in both groups during the study period. The purpose of our biomarker-based exploratory analysis was to determine whether long-term platelet inhibition may be associated with platelet adaptation...
June 12, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28608115/phase-i-trial-of-antigen-targeted-autologous-dendritic-cell-based-vaccine-with-in-vivo-activation-of-inducible-cd40-for-advanced-prostate-cancer
#17
Guru Sonpavde, John D McMannis, Yu Bai, Mamatha R Seethammagari, Joan M C Bull, Victoria Hawkins, Theresa K Dancsak, Natasha Lapteva, Jonathan M Levitt, Annemarie Moseley, David M Spencer, Kevin M Slawin
This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation...
June 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28605029/the-pancreatic-cancer-microenvironment-a-true-double-agent
#18
REVIEW
Laleh G Melstrom, Marcela D Salazar, Don J Diamond
The tumor microenvironment in pancreatic cancer is a complex balance of pro- and anti-tumor components. The dense desmoplasia consists of immune cells, extracellular matrix, growth factors, cytokines, and cancer associated fibroblasts (CAF) or pancreatic stellate cells (PSC). There are a multitude of targets including hyaluronan, angiogenesis, focal adhesion kinase (FAK), connective tissue growth factor (CTGF), CD40, chemokine (C-X-C motif) receptor 4 (CXCR-4), immunotherapy, and Vitamin D. The developing clinical therapeutics will be reviewed...
June 12, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28602123/paraoxonase-1-and-myeloperoxidase-correlate-with-vascular-biomarkers-in-overweight-patients-with-newly-diagnosed-untreated-hyperlipidaemia
#19
Anita Szentpéteri, Noémi Zsíros, Viktória E Varga, Hajnalka Lőrincz, Mónika Katkó, Ildikó Seres, Péter Fülöp, György Paragh, Mariann Harangi
BACKGROUND: In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified. PATIENTS AND METHODS: Serum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls...
June 12, 2017: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/28597963/mir-181a-and-mir-150-regulate-dendritic-cell-immune-inflammatory-responses-and-cardiomyocyte-apoptosis-via-targeting-jak1-stat1-c-fos-pathway
#20
Jianbing Zhu, Kang Yao, Junjie Guo, Hongtao Shi, Leilei Ma, Qian Wang, Haibo Liu, Wei Gao, Aijun Sun, Yunzeng Zou, Junbo Ge
The immune inflammatory response plays a crucial role in many cardiac pathophysiological processes, including ischaemic cardiac injury and the post-infarction repair process. MicroRNAs (miRNAs) regulate the development and function of dendritic cells (DCs), which are key players in the initiation and regulation of immune responses; however, the underlying regulatory mechanisms remain unclear. Here, we used the supernatants of necrotic primary cardiomyocytes (Necrotic-S) to mimic the myocardial infarction (MI) microenvironment to investigate the role of miRNAs in the regulation of DC-mediated inflammatory responses...
June 9, 2017: Journal of Cellular and Molecular Medicine
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