keyword
MENU ▼
Read by QxMD icon Read
search

Syk t cell

keyword
https://www.readbyqxmd.com/read/28209719/adaptive-nk-cells-can-persist-in-patients-with-gata2-mutation-depleted-of-stem-and-progenitor-cells
#1
Heinrich Schlums, Moonjung Jung, Hongya Han, Jakob Theorell, Venetia Bigley, Samuel C C Chiang, David S J Allan, Jan K Davidson-Moncada, Rachel E Dickinson, Tim D Holmes, Amy P Hsu, Danielle Townsley, Thomas Winkler, Weixin Wang, Pål Aukrust, Ingvild Nordøy, Katherine R Calvo, Steve M Holland, Matthew Collin, Cynthia E Dunbar, Yenan T Bryceson
Heterozygous GATA2 mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and NK cells. Nonetheless, in a proportion of patients carrying GATA2 mutation, NK cells persist. We found that peripheral blood NK cells in symptomatic patients uniformly lacked expression of the transcription factor PLZF, as well as expression of intracellular signaling proteins FcϵRγ, SYK, and EAT-2 in a variegated manner...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28154084/lymphocyte-activation-gene-3-a-novel-therapeutic-target-in-chronic-lymphocytic-leukemia
#2
Mika Shapiro, Yair Herishanu, Ben-Zion Katz, Nili Dezorella, Clare Sun, Sigi Kay, Aaron Polliack, Irit Avivi, Adrian Wiestner, Chava Perry
A novel therapeutic approach in cancer, attempting to stimulate host anti-tumor immunity, involves blocking of immune checkpoints. LAG3 is an immune checkpoint receptor expressed on activated/exhausted T-cells. When engaged by MHC class II molecules, LAG3 negatively regulates T-cell function thereby contributing to tumor escape. Intriguingly, a soluble LAG3 variant activates both immune and malignant MHC class II-presenting cells. In this study, we examined the role of LAG3 in the pathogenesis of chronic lymphocytic leukemia, an MHC class II-presenting malignancy, and show that chronic lymphocytic leukemia cells express and secrete LAG3...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28111009/glomerular-common-gamma-chain-confers-b-and-t-cell-independent-protection-against-glomerulonephritis
#3
Yosu Luque, Dominique Cathelin, Sophie Vandermeersch, Xiaoli Xu, Julie Sohier, Sandrine Placier, Yi-Chun Xu-Dubois, Kevin Louis, Alexandre Hertig, Jean-Christophe Bories, Florence Vasseur, Fabien Campagne, James P Di Santo, Christian Vosshenrich, Eric Rondeau, Laurent Mesnard
Crescentic glomerulonephritis is a life-threatening renal disease that has been extensively studied by the experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) model. Although T cells have a significant role in this model, athymic/nude mice and rats still develop severe renal disease. Here we further explored the contribution of intrinsic renal cells in the development of T-cell-independent GN lesions. Anti-GBM-GN was induced in three strains of immune-deficient mice (Rag2(-/-), Rag2(-/-)Il2rg(-/-), and Rag2(-/-)Il2rb(-/-)) that are devoid of either T/B cells or T/B/NK cells...
January 19, 2017: Kidney International
https://www.readbyqxmd.com/read/28100106/systemic-lupus-erythematosus-in-the-light-of-the-regulatory-effects-of-galectin-1-on-t-cell-function
#4
Á Hornung, É Monostori, L Kovács
Galectin-1 is an endogenous immunoregulatory lectin-type protein. Its most important effects are the inhibition of the differentiation and cytokine production of Th1 and Th17 cells, and the induction of apoptosis of activated T-cells. Galectin-1 has been identified as a key molecule in antitumor immune surveillance, and data are accumulating about the pathogenic role of its deficiency, and the beneficial effects of its administration in various autoimmune disease models. Initial animal and human studies strongly suggest deficiencies in both galectin-1 production and responsiveness in systemic lupus erythematosus (SLE) T-cells...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28011996/the-kinase-inhibitors-r406-and-gs-9973-impair-t-cell-functions-and-macrophage-mediated-anti-tumor-activity-of-rituximab-in-chronic-lymphocytic-leukemia-patients
#5
Ana Colado, María Belén Almejún, Enrique Podaza, Denise Risnik, Carmen Stanganelli, Esteban Enrique Elías, Patricia Dos Santos, Irma Slavutsky, Horacio Fernández Grecco, María Cabrejo, Raimundo Fernando Bezares, Mirta Giordano, Romina Gamberale, Mercedes Borge
Small molecules targeting kinases involved in B cell receptor signaling are showing encouraging clinical activity in chronic lymphocytic leukemia (CLL) patients. Fostamatinib (R406) and entospletinib (GS-9973) are ATP-competitive inhibitors designed to target spleen tyrosine kinase (Syk) that have shown clinical activity with acceptable toxicity in trials with CLL patients. Preclinical studies with these inhibitors in CLL have focused on their effect in patient-derived leukemic B cells. In this work we show that clinically relevant doses of R406 and GS-9973 impaired the activation and proliferation of T cells from CLL patients...
April 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27966556/mv140-a-sublingual-polyvalent-bacterial-preparation-to-treat-recurrent-urinary-tract-infections-licenses-human-dendritic-cells-for-generating-th1-th17-and-il-10-responses-via-syk-and-myd88
#6
C Benito-Villalvilla, C Cirauqui, C M Diez-Rivero, M Casanovas, J L Subiza, O Palomares
Recurrent urinary tract infections (RUTIs) are one of the most common bacterial infectious diseases, especially in women. Antibiotics remain the mainstay of treatment, but their overuse is associated with antibiotic-resistant infections and deleterious effects in the microbiota. Therefore, alternative approaches are fully demanded. Sublingual immunization with MV140 (Uromune), a polyvalent bacterial preparation (PBP) of whole heat-inactivated bacteria, demonstrated clinical efficacy for the treatment of RUTIs, but the involved immunological mechanisms remain unknown...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27935477/regulation-of-b-cell-fate-by-chronic-activity-of-the-ige-b-cell-receptor
#7
Zhiyong Yang, Marcus J Robinson, Xiangjun Chen, Geoffrey A Smith, Jack Taunton, Wanli Liu, Christopher D C Allen
IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE(+) B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help. This antigen-independent PC differentiation involved multiple IgE domains and Syk, CD19, BLNK, Btk, and IRF4. Disruption of BCR signaling in mice led to consistently exaggerated IgE(+) germinal center (GC) B cell but variably increased PC responses...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27895176/the-syk-nfat-il-2-pathway-in-dendritic-cells-is-required-for-optimal-sterile-immunity-elicited-by-alum-adjuvants
#8
Hanif Javanmard Khameneh, Adrian W S Ho, Roberto Spreafico, Heidi Derks, Hazel Q Y Quek, Alessandra Mortellaro
Despite a long history and extensive usage of insoluble aluminum salts (alum) as vaccine adjuvants, the molecular mechanisms underpinning Ag-specific immunity upon vaccination remain unclear. Dendritic cells (DCs) are crucial initiators of immune responses, but little is known about the molecular pathways used by DCs to sense alum and, in turn, activate T and B cells. In this article, we show that alum adjuvanticity requires IL-2 specifically released by DCs, even when T cell secretion of IL-2 is intact. We demonstrate that alum, as well as other sterile particulates, such as uric acid crystals, induces DCs to produce IL-2 following initiation of actin-mediated phagocytosis that leads to Src and Syk kinase activation, Ca(2+) mobilization, and calcineurin-dependent activation of NFAT, the master transcription factor regulating IL-2 expression...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27890932/il-10-production-by-cll-cells-is-enhanced-in-the-anergic-ighv-mutated-subset-and-associates-with-reduced-dna-methylation-of-the-il10-locus
#9
S Drennan, A D'Avola, Y Gao, C Weigel, E Chrysostomou, A J Steele, T Zenz, C Plass, P W Johnson, A P Williams, G Packham, F K Stevenson, C C Oakes, F Forconi
Chronic lymphocytic leukemias (CLLs) with unmutated (U-CLL) or mutated (M-CLL) IGHV have variable features of immunosuppression, possibly influenced by those CLL cells activated to produce interleukin 10 (IL-10). The two subsets differ in their levels of anergy, defined by low surface immunoglobulin M levels/signaling capacity, and in their DNA methylation profile, particularly variable in M-CLL. We have now found that levels of IL-10 produced by activated CLL cells were highly variable. Levels were higher in M-CLL than in U-CLL and correlated with anergy...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27888629/inhibition-of-bcr-signaling-using-the-syk-inhibitor-tak-659-prevents-stroma-mediated-signaling-in-chronic-lymphocytic-leukemia-cells
#10
Noelia Purroy, Júlia Carabia, Pau Abrisqueta, Leire Egia, Meritxell Aguiló, Cecilia Carpio, Carles Palacio, Marta Crespo, Francesc Bosch
Proliferation and survival of chronic lymphocytic leukemia (CLL) cells depend on microenvironmental signals coming from lymphoid organs. One of the key players involved in the crosstalk between CLL cells and the microenvironment is the B-cell receptor (BCR). Syk protein, a tyrosine kinase essential for BCR signaling, is therefore a rational candidate for targeted therapy in CLL. Against this background, we tested the efficacy of the highly specific Syk inhibitor TAK-659 in suppressing the favorable signaling derived from the microenvironment...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27837109/characterization-of-the-syk-dependent-t-cell-signaling-response-to-an-altered-peptide
#11
Jeoung-Eun Park, Jeffrey A Rotondo, David L Cullins, David D Brand, Ae-Kyung Yi, John M Stuart, Andrew H Kang, Linda K Myers
Rheumatoid arthritis is an autoimmune disorder characterized by T cell dysregulation. We have shown that an altered peptide ligand (A9) activates T cells to use an alternate signaling pathway that is dependent on FcRγ and spleen tyrosine kinase, resulting in downregulation of inflammation. In the experiments described in this study, we have attempted to determine the molecular basis of this paradox. Three major Src family kinases found in T cells (Lck, Fyn, and Lyn) were tested for activation following stimulation by A9/I-A(q) Unexpectedly we found they are not required for T cell functions induced by A9/I-A(q), nor are they required for APL stimulation of cytokines...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27756749/phosphodiesterase-4-inhibitors-have-wide-ranging-activity-in-b-cell-malignancies
#12
REVIEW
Jeffrey D Cooney, Ricardo C T Aguiar
Phosphodiesterase 4 (PDE4) inhibition restores the suppressive effects of 3',5'-cyclic adenosine monophosphate in lymphocytes. In this concise review, we detail how PDE4 inhibition downmodulates the B-cell receptor (BCR)-related kinases spleen tyrosine kinase and phosphatidylinositol 3-kinase and inhibits vascular endothelial growth factor A secretion by tumor cells, inducing cancer cell apoptosis and blocking angiogenesis in the microenvironment. We describe the successful clinical repurposing of PDE4 inhibitors in B-cell malignancies, and propose that given their anti-inflammatory/immunomodulatory activity, these agents will suppress BCR signals without the toxicity associated with other targeted biological doublets...
December 22, 2016: Blood
https://www.readbyqxmd.com/read/27621811/phosphocholine-containing-ligands-direct-crp-induction-of-m2-macrophage-polarization-independent-of-t-cell-polarization-implication-for-chronic-inflammatory-states
#13
JoAnn Trial, Katarzyna A Cieslik, Mark L Entman
INTRODUCTION: We studied monocyte transendothelial migration and subsequent polarization into M1/M2 macrophages in response to C-reactive protein (CRP) with two disease-related ligands: (1) phosphocholine (PC) and (2) multilamellar liposomes containing both unoxidized and oxidized forms of the lipid, phosphatidylcholine. These ligands differ in biological origin: PC is present on bacterial cell walls while oxidized lipids are present in atherogenic lipids. METHODS: We used an in vitro model of human monocyte transendothelial migration and assessed the polarization of monocytes and T cells and signaling through Fcγ receptors in monocytes...
September 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27492902/dectin-1-activated-dendritic-cells-trigger-potent-antitumour-immunity-through-the-induction-of-th9-cells
#14
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
https://www.readbyqxmd.com/read/27484700/mapping-epigenetic-changes-to-the-host-cell-genome-induced-by-burkholderia-pseudomallei-reveals-pathogen-specific-and-pathogen-generic-signatures-of-infection
#15
Deniz Cizmeci, Emma L Dempster, Olivia L Champion, Sariqa Wagley, Ozgur E Akman, Joann L Prior, Orkun S Soyer, Jonathan Mill, Richard W Titball
The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have been reported. We assessed genome-wide patterns of DNA methylation in human macrophage-like U937 cells following infection with Burkholderia pseudomallei, an intracellular bacterial pathogen and the causative agent of human melioidosis. Our analyses revealed significant changes in host cell DNA methylation, at multiple CpG sites in the host cell genome, following infection. Infection induced differentially methylated probes (iDMPs) showing the greatest changes in DNA methylation were found to be in the vicinity of genes involved in inflammatory responses, intracellular signalling, apoptosis and pathogen-induced signalling...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27456487/fc%C3%AE-riib-independent-mechanisms-controlling-membrane-localization-of-the-inhibitory-phosphatase-ship-in-human-b-cells
#16
Samantha D Pauls, Arnab Ray, Sen Hou, Andrew T Vaughan, Mark S Cragg, Aaron J Marshall
SHIP is an important regulator of immune cell signaling that functions to dephosphorylate the phosphoinositide phosphatidylinositol 3,4,5-trisphosphate at the plasma membrane and mediate protein-protein interactions. One established paradigm for SHIP activation involves its recruitment to the phospho-ITIM motif of the inhibitory receptor FcγRIIB. Although SHIP is essential for the inhibitory function of FcγRIIB, it also has critical modulating functions in signaling initiated from activating immunoreceptors such as B cell Ag receptor...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27449326/curdlan-activates-dendritic-cells-through-dectin-1-and-toll-like-receptor-4-signaling
#17
Hyung Sook Kim, Ki Hwan Park, Hong Kyung Lee, Ji Sung Kim, Yong Guk Kim, Jae Hee Lee, Ki Hun Kim, Jieun Yun, Bang Yeon Hwang, Jin Tae Hong, Youngsoo Kim, Sang-Bae Han
Curdlan, a β-1,3-glucan isolated from Alcaligenes faecalis, is an agonist of dectin-1 in various immune cells, including dendritic cells (DCs). However, whether curdlan also activates DCs through other receptors remains unknown. In this study, we found that curdlan activates DCs through dectin-1 and toll-like receptor 4 (TLR4). Curdlan increased the expression levels of surface molecules (CD40, CD80, CD86, and MHC-I/II), the production of cytokines (IL-12, IL-1β, TNF-α, and IFN-β), migration toward MIP-3β, and allogeneic T cell stimulation activity of DCs...
October 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27443285/slp76-integrates-into-the-b-cell-receptor-signaling-cascade-in-chronic-lymphocytic-leukemia-cells-and-is-associated-with-an-aggressive-disease-course
#18
Nili Dezorella, Ben-Zion Katz, Mika Shapiro, Aaron Polliack, Chava Perry, Yair Herishanu
I In the last decade, the B-cell receptor has emerged as a pivotal stimulus in the pathogenesis of chronic lymphocytic leukemia, and a very feasible therapeutic target in this disease. B-cell receptor responsiveness in chronic lymphocytic leukemia cells is heterogeneous among patients and correlates with aggressiveness of the disease. Here we show, for the first time, that SLP76, a key scaffold protein in T-cell receptor signaling, is ectopically expressed in chronic lymphocytic leukemia cells, with variable levels among patients, and correlates positively with unmutated immunoglobulin heavy chain variable gene status and ZAP-70 expression...
December 2016: Haematologica
https://www.readbyqxmd.com/read/27384937/imaging-spatiotemporal-activities-of-zap-70-in-live-t-cells-using-a-fret-based-biosensor
#19
Kaitao Li, Xue Xiang, Jie Sun, Hai-Tao He, Jianhua Wu, Yingxiao Wang, Cheng Zhu
The zeta-chain-associated protein kinase 70 kDa (ZAP-70), a member of the spleen tyrosine kinase (Syk) family, plays an essential role in early T cell receptor (TCR) signaling. Defects in ZAP-70 lead to impaired thymocyte development and peripheral T cell activation. To better understand its activation dynamics and regulation, we visualized ZAP-70 activities in single live T cells with a Förster resonance energy transfer (FRET)-based biosensor, which was designed for probing kinase activities of the Syk family...
December 2016: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/27287425/lenalidomide-induces-interleukin-21-production-by-t-cells-and-enhances-il21-mediated-cytotoxicity-in-chronic-lymphocytic-leukemia-b-cells
#20
Rebekah L Browning, William H Byrd, Nikhil Gupta, Jeffrey Jones, Xiaokui Mo, Erin Hertlein, Lianbo Yu, Natarajan Muthusamy, John C Byrd
The immunomodulatory drug lenalidomide has demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL), despite a lack of direct cytotoxic effects in vitro The mechanism of lenalidomide efficacy in vivo is thought to occur via a combination of enhanced immune activity and an alteration of tumor cell-microenvironment interactions. We demonstrate in whole blood from patients with CLL that lenalidomide significantly depletes malignant B cells. Lenalidomide also induced production of interleukin-21 (IL21) and its mRNA in T cells from patients with CLL...
August 2016: Cancer Immunology Research
keyword
keyword
111404
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"