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Ehteramolsadat Hosseini, Mehran Ghasemzadeh, Fatemeh Nassaji, Zeynab Pirmohammad Jamaat
Platelet storage is associated with deleterious changes leading to the loss of platelet reactivity and response. During storage, platelets experience increased expression and shedding of P-selectin and CD40L as specific markers of platelet activation, whereas GPIbα decreases due to ectodomain shedding. As an important adhesive receptor, GPVI contributes significantly to thrombus formation while its expression and shedding levels during storage of platelet products have not been well characterized yet. This study investigated the modulation of GPVI during platelet storage...
October 25, 2016: Platelets
Dana Tedesco, Manoj Thapa, Sanjeev Gumber, Elizabeth J Elrod, Khalidur Rahman, Chris C Ibegbu, Joseph F Magliocca, Andrew B Adams, Frank Anania, Arash Grakoui
: Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to non-functional intrahepatic CD8+ T cell responses. In light of dampened CD8+ T cell responses, liver disease often manifests systemically as Ig-related syndromes due to aberrant B cell functions. These two opposing yet co-existing phenomena implicate the potential of altered CD4+ T cell help. Elevated CD4+ Foxp3+ T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Patrícia Napoleão, Ekaterina Potapova, Sara Moleirinho, Carlota Saldanha, António Messias
AIM: Soluble CD40 ligand (sCD40L) has been considered as a marker of thrombosis and inflammation in several diseases, including sepsis. Recent studies challenge this view and point to a role of sCD40L in vascular and endothelial function. An indication of that association in sepsis has not been obtained so far. Therefore, herein we evaluated association between sCD40L and markers of hemorheology and inflammation on context of septic shock. METHODS: Time-changes of sCD40L levels over 72 hours of Intensive Care Unit (ICU) internment were assessed in 22 patients with septic shock and compared with 36 healthy volunteers...
October 20, 2016: Clinical Hemorheology and Microcirculation
Jennifer L Gardell, David C Parker
The delivery of T-cell help to B cells is antigen-specific, MHC-restricted, and CD40L (CD154) dependent. It has been thought that when a T cell recognizes an antigen-presenting B cell, CD40L expressed on the T-cell surface engages with CD40 on the surface of B cells as long as the cells remain conjugated. To study this, we added fluorescently labeled anti-CD40L antibody during overnight incubation of antigen-presenting B cells with antigen-specific T cells. We discovered that CD40L does not remain on the surface of the T cell, but it is transferred to and endocytosed by B cells receiving T-cell help...
October 18, 2016: European Journal of Immunology
H Vroman, I M Bergen, B W S Li, J A C van Hulst, M Lukkes, D van Uden, R W Hendriks, M Kool
BACKGROUND: Chronic exposure to environmental triggers, such as house dust mite (HDM), drives T helper 2 (Th2) cell-mediated asthma. Recent evidence has shown that B-T cell interaction, and in particular germinal center reactions and follicular T helper (Tfh) cells are required for the development of eosinophilic airway inflammation in HDM-driven models containing a sensitization and challenge phase. Whether B-T cell interactions are essential for pulmonary eosinophilic inflammation following chronic allergen provocation remains unknown...
October 15, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
E Balada, L Felip, J Ordi-Ros, M Vilardell-Tarrés
We evaluated the transcriptional expression of DUSP23 in CD4+ T cells from 30 SLE patients and 30 healthy controls. DUSP23 mRNA levels were considerably higher in the patients group: 1,490 ± 1,713 versus 294,1 ± 204,2. None association was found between DUSP23 mRNA expression and the presence of typical serological and clinical parameters associated to SLE. Meaningful statistical values were obtained in the patients group between the levels of DUSP23 and ITGAL, PRF1, and CD40L. Similarly, transcript levels of different DNA methylation-related enzymes (DNMT1, DNMT3A, DNMT3B, MBD2, and MBD4) were also positively correlated to the expression of DUSP23...
October 13, 2016: Clinical and Experimental Immunology
Angela Berzi, Stefania Ordanini, Ben Joosten, Daria Trabattoni, Alessandra Cambi, Anna Bernardi, Mario Clerici
DC-SIGN, a C-type lectin mainly expressed by DCs, mediates antigen uptake and can induce specific immune responses, depending on the ligand involved. Owing to these properties, DC-SIGN is an attracting target for approaches aimed at tailoring the immune response towards specific immunologic outcomes. A multivalent DC-SIGN ligand (Polyman26), containing at its core a fluorescent "rod-like" spacer and able to inhibit DC-SIGN mediated HIV infection in nanomolar concentration, has been recently developed by our group...
October 13, 2016: Scientific Reports
Ilaria Marigo, Serena Zilio, Giacomo Desantis, Bernhard Mlecnik, Andrielly H R Agnellini, Stefano Ugel, Maria Stella Sasso, Joseph E Qualls, Franz Kratochvill, Paola Zanovello, Barbara Molon, Carola H Ries, Valeria Runza, Sabine Hoves, Amélie M Bilocq, Gabriela Bindea, Emilia M C Mazza, Silvio Bicciato, Jérôme Galon, Peter J Murray, Vincenzo Bronte
No abstract text is available yet for this article.
October 10, 2016: Cancer Cell
Xiaonan Zhong, Honghao Wang, Zhiwei Ye, Wei Qiu, Zhengqi Lu, Rui Li, Yaqing Shu, Yanyu Chang, Xueqiang Hu
It is believed that auto-inflammatory activity, including cellular and humoral immunity responses, especially T cell-B cell collaboration, is one of the most important components of the pathogenesis of inflammatory demyelinating disease. CD40L is critical for T cell-B cell collaboration. Actually, serum CD40L levels have been shown to increase in MS. In the present study, serum CD40L levels were measured by an enzyme-linked immunosorbent assay (ELISA) in NMO (n=27) and MS (n=19) patients and controls (n=14)...
October 15, 2016: Journal of Neuroimmunology
Laurence C Menard, Sium Habte, Waldemar Gonsiorek, Deborah Lee, Dana Banas, Deborah A Holloway, Nataly Manjarrez-Orduno, Mark Cunningham, Dawn Stetsko, Francesca Casano, Selena Kansal, Patricia M Davis, Julie Carman, Clarence K Zhang, Ferva Abidi, Richard Furie, Steven G Nadler, Suzanne J Suchard
Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease driven by both innate and adaptive immune cells. African Americans tend to present with more severe disease at an earlier age compared with patients of European ancestry. In order to better understand the immunological differences between African American and European American patients, we analyzed the frequencies of B cell subsets and the expression of B cell activation markers from a total of 68 SLE patients and 69 normal healthy volunteers...
June 16, 2016: JCI Insight
Matthew D Blunt, Stefan Koehrer, Rachel Dobson, Marta Larrayoz, Sarah Wilmore, Alice Hayman, Jack Parnell, Lindsay D Smith, Andrew Davies, Peter Wm Johnson, Pamela B Conley, Anjali Pandey, Jonathan C Strefford, Freda K Stevenson, Graham Packham, Francesco Forconi, Greg P Coffey, Jan Burger, Andrew J Steele
PURPOSE: B-cell receptor (BCR)-associated kinase inhibitors such as ibrutinib have revolutionised the treatment of chronic lymphocytic leukemia (CLL). However, these agents are not curative and resistance is already emerging in a proportion of patients. Interleukin-4 (IL-4), expressed in CLL lymph nodes, can augment BCR-signalling and reduce the effectiveness of BCR-kinase inhibitors. Therefore simultaneous targeting of the IL-4- and BCR-signalling pathways by cerdulatinib, a novel dual Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve treatment responses in patients...
October 3, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
David Chiron, Céline Bellanger, Antonin Papin, Benoit Tessoulin, Christelle Dousset, Sophie Maiga, Anne Moreau, Julie Esbelin, Valérie Trichet, Selina Chen-Kiang, Philippe Moreau, Cyrille Touzeau, Steven Le Gouill, Martine Amiot, Catherine Pellat-Deceunynck
Mantle cell lymphoma (MCL) accumulates in lymphoid organs but disseminates early on in extranodal tissues. Although proliferation remains located in lymphoid organs only, suggesting a major role of the tumor ecosystem, few studies have assessed MCL microenvironment. We therefore cocultured primary circulating MCL cells from 21 patients several weeks ex vivo with stromal or lymphoid-like (CD40L) cells to determine which interactions could support their proliferation. We showed that coculture with lymphoid-like cells, but not stromal cells, induced cell-cycle progression, which was amplified by MCL-specific cytokines (IGF-1, BAFF, IL-6, IL-10)...
October 3, 2016: Blood
Roxanne Coronel, Desyree M Jesus, Lucia Dalle Ore, Joe S Mymryk, Laura Hertel
Oral mucosal Langerhans cells (LC) are likely to play important roles in host defense against infection by human cytomegalovirus (CMV). We previously showed that in vitro-differentiated immature LC (iLC) populations contain smaller amounts of infected cells but produce higher yields than mature LC (mLC) cultures, obtained by iLC stimulation with fetal bovine serum (FBS), CD40 ligand (CD40L) and lipopolysaccharide (LPS). Here, we sought to determine if exposure to select stimuli can improve LC permissiveness to infection, if specific components of the mLC cocktail are responsible for lowering viral yields, if this is due to defects in progeny production or release, and if these restrictions are also effective against reactivated virus...
2016: Frontiers in Microbiology
Maria Sole Chimenti, Alberto Bergamini, Paola Triggianese, Maria Domenica Guarino, Gianfranco Gigliucci, Paola Conigliaro, Carlo Perricone, Roberto Perricone
OBJECTIVES: To investigate the presence of immunoglobulin-like transcript (ILT)4 and costimulatory proteins (CD40, CD80 and CD86), as well as tumour necrosis factor (TNF)-α production in antigen-presenting cells (APCs) from patients with psoriatic arthritis, before and after treatment with the antitumour necrosis factor-α therapy, adalimumab. METHODS: Peripheral blood monocytes from patients with psoriatic arthritis and healthy controls were cultured with CD40 ligand (CD40L) to stimulate differentiation to APCs...
September 2016: Journal of International Medical Research
Edoardo Vitolo, Eleonora Santini, Marta Seghieri, Livia Giannini, Fabio Coppedè, Chiara Rossi, Angela Dardano, Anna Solini
BACKGROUND: Several patients encompass a scarce weight loss after Roux-en-Y gastric bypass (RYGB). As such event is not related to surgical complications, finding markers able to identify "well responders" and to predict weight loss outcome is clinically relevant. Ghrelin regulates appetite and energy balance. Common single nucleotide polymorphisms (SNPs) in its encoding genes have been associated with body weight regulation. Other peptides involved in satiety modulation, like the CD40/CD40L complex, are less explored...
September 28, 2016: Obesity Surgery
Alberto C Guardo, Patrick Tjok Joe, L Miralles, M E Bargalló, B Mothe, A Krasniqi, C Heirman, F García, Kris Thielemans, Christian Brander, Joeri L Aerts, Montserrat Plana
BACKGROUND: The development of a prophylactic vaccine against HIV-1 has so far not been successful. Therefore, attention has shifted more and more towards the development of novel therapeutic vaccines. Here, we evaluated a new mRNA based therapeutic vaccine against HIV-1 encoding activation signals (TriMix: CD40L+CD70+caTLRA4) combined with rationally selected antigenic sequences (HTI sequence: comprised of 16 joined fragments from Gag, Pol, Vif and Nef). METHODS: For this purpose, PBMC from HIV-1-infected individuals on cART, lymph node explants from non-infected humans and splenocytes from immunized mice were collected and several immune functions were measured...
September 24, 2016: AIDS
Stefano Alivernini, Mariola Kurowska-Stolarska, Barbara Tolusso, Roberta Benvenuto, Aziza Elmesmari, Silvia Canestri, Luca Petricca, Antonella Mangoni, Anna Laura Fedele, Clara Di Mario, Maria Rita Gigante, Elisa Gremese, Iain B McInnes, Gianfranco Ferraccioli
MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD(-)CD27(-) memory B-cell population in ACPA(+) RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU...
September 27, 2016: Nature Communications
Maren Feist, Judith Kemper, Franziska Taruttis, Thorsten Rehberg, Julia C Engelmann, Wolfram Gronwald, Michael Hummel, Rainer Spang, Dieter Kube
A network of autocrine and paracrine signals defines B cell homeostasis and is thought to be involved in transformation processes. Investigating interactions of these microenvironmental factors and their relation to proto-oncogenes as c-Myc (MYC) is fundamental to understand the biology of B cell lymphoma. Therefore, B cells with conditional MYC expression were stimulated with CD40L, insulin-like growth factor 1, α-IgM, Interleukin-10 (IL10) and CpG alone or in combination. The impact of forty different interventions on cell proliferation was investigated in MYC deprived cells and calculated by linear regression...
September 26, 2016: International Journal of Cancer. Journal International du Cancer
Li-Dan Zhao, Di Liang, Xiang-Ni Wu, Yang Li, Jing-Wen Niu, Chen Zhou, Li Wang, Hua Chen, Wen-Jie Zheng, Yun-Yun Fei, Fu-Lin Tang, Yong-Zhe Li, Feng-Chun Zhang, Wei He, Xue-Tao Cao, Xuan Zhang
Aberrant expression of CXCR4 has been indicated to play a role in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanism of CXCR4 dysregulation in SLE is unclear. This study is aimed to explore the clinical significance and possible mechanisms of abnormal CXCR4 expression on B cells from patients with untreated SLE. Expression of CXCR4 on peripheral B cells was determined by flow cytometry and western blotting. Freshly isolated B cells were cultured with exogenous interleukin 21(IL-21) in the presence or absence of CD40 ligand (CD40L) plus anti-IgM antibody (aIgM), and changes in CXCR4 expression were detected...
September 26, 2016: Cellular & Molecular Immunology
Shahnawaz Ali Bhat, Ruby Goel, Rakesh Shukla, Kashif Hanif
Studies have demonstrated separately that hypertension is associated with platelet activation in the periphery (resulting in accumulation and localized inflammatory response) and glial activation in the brain. We investigated the contribution of platelets in brain inflammation, particularly glial activation in vitro and in a rat model of hypertension. We found that HTN increased the expression of adhesion molecules like JAM-1, ICAM-1, and VCAM-1 on brain endothelium and resulted in the deposition of platelets in the brain...
September 19, 2016: Brain, Behavior, and Immunity
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