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https://www.readbyqxmd.com/read/28677817/inhibition-of-the-hdac-suv39-g9a-pathway-restores-the-expression-of-dna-damage-dependent-major-histocompatibility-complex-class%C3%A2-i-related-chain%C3%A2-a%C3%A2-and%C3%A2-b-in-cancer-cells
#1
Nakako Izumi Nakajima, Atsuko Niimi, Mayu Isono, Takahiro Oike, Hiro Sato, Takashi Nakano, Atsushi Shibata
Immunotherapy is expected to be promising as a next generation cancer therapy. Immunoreceptors are often activated constitutively in cancer cells, however, such levels of ligand expression are not effectively recognized by the native immune system due to tumor microenvironmental adaptation. Studies have demonstrated that natural-killer group 2, member D (NKG2D), a major activating immunoreceptor, responds to DNA damage. The upregulation of major histocompatibility complex class I-related chain A and B (MICA/B) (members of NKG2D ligands) expression after DNA damage is associated with NK cell-mediated killing of cancer cells...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28675212/enzymatic-self-assembly-of-an-immunoreceptor-tyrosine-based-inhibitory-motif-itim
#2
Natsuko Yamagata, Xiaoyi Chen, Jie Zhou, Jie Li, Xuewen Du, Bing Xu
Here we show the first example of an immunoreceptor tyrosine-based inhibitory motif (ITIM), LYYYYL, as well as its enantiomeric or retro-inverso peptide, to self-assemble in water via enzyme-instructed self-assembly. Upon enzymatic dephosphorylation, the phosphohexapeptides become hexapeptides, which self-assemble in water to result in supramolecular hydrogels. This work illustrates a new approach to design bioinspired soft materials from a less explored, but important pool of immunomodulatory peptides.
July 4, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28652325/transmembrane-features-governing-fc-receptor-cd16a-assembly-with-cd16a-signaling-adaptor-molecules
#3
Alfonso Blázquez-Moreno, Soohyung Park, Wonpil Im, Melissa J Call, Matthew E Call, Hugh T Reyburn
Many activating immunoreceptors associate with signaling adaptor molecules like FcεR1γ or CD247. FcεR1γ and CD247 share high sequence homology and form disulphide-linked homodimers that contain a pair of acidic aspartic acid residues in their transmembrane (TM) domains that mediate assembly, via interaction with an arginine residue at a similar register to these aspartic acids, with the activating immunoreceptors. However, this model cannot hold true for receptors like CD16A, whose TM domains do not contain basic residues...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28650106/dok3-modulates-bone-remodeling-by-negatively-regulating-osteoclastogenesis-and-positively-regulating-osteoblastogenesis
#4
Xiaofeng Cai, Junjie Xing, Courtney L Long, Qisheng Peng, Mary Beth Humphrey
Osteoclastogenesis is essential for bone remodeling and normal skeletal maintenance. RANKL promotes osteoclast differentiation and function but requires costimulation of immunoreceptor tyrosine-based activation motif (ITAM)-coupled immunoreceptors. Triggering receptor expressed on myeloid cells-2 (TREM2) coupled to ITAM-adaptor protein DNAX activation protein 12kDA (DAP12) provides costimulation of intracellular calcium signaling during osteoclastogenesis. Previously, we found that downstream of kinase-3 (DOK3) physically associates with DAP12 to inhibit toll-like receptor (TLR)-induced inflammatory signaling in macrophages...
June 26, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28646116/tonic-b-cell-receptor-signaling-in-diffuse-large-b-cell-lymphoma
#5
Ondrej Havranek, Jingda Xu, Stefan Köhrer, Zhiqiang Wang, Lisa Becker, Justin M Comer, Jared Henderson, Wencai Ma, John Man Chun Ma, Jason R Westin, Dipanjan Ghosh, Nicholas Shinners, Luhong Sun, Allen F Yi, Anusha R Karri, Jan A Burger, Tomasz Zal, R Eric Davis
We used CRISPR/Cas9-mediated genomic modification to investigate B-cell receptor (BCR) signaling in cell lines of diffuse large B-cell lymphoma (DLBCL). Three manipulations that altered BCR genes without affecting surface BCR levels showed that BCR signaling differs between the germinal center B-cell (GCB) subtype, which is insensitive to BTK inhibition by ibrutinib, and the activated B-cell (ABC) subtype. Replacing antigen-binding BCR regions had no effect on BCR signaling in GCB-DLBCL lines, reflecting this subtype's exclusive use of tonic BCR signaling...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28638976/lilrb-receptor-mediated-regulation-of-myeloid-cell-maturation-and-function
#6
REVIEW
William van der Touw, Hui-Ming Chen, Ping-Ying Pan, Shu-Hsia Chen
The leukocyte immunoglobulin-like receptor (LILR) family comprises a set of paired immunomodulatory receptors expressed among human myeloid and lymphocyte cell populations. While six members of LILR subfamily A (LILRA) associate with membrane adaptors to signal via immunoreceptor tyrosine-based activating motifs (ITAM), LILR subfamily B (LILRB) members signal via multiple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIM). Ligand specificity of some LILR family members has been studied in detail, but new perspective into the immunoregulatory aspects of this receptor family in human myeloid cells has been limited...
June 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28629373/blimp-1-impairs-t-cell-function-via-upregulation-of-tigit-and-pd-1-in-patients-with-acute-myeloid-leukemia
#7
Liuluan Zhu, Yaxian Kong, Jianhong Zhang, David F Claxton, W Christopher Ehmann, Witold B Rybka, Neil D Palmisiano, Ming Wang, Bei Jia, Michael Bayerl, Todd D Schell, Raymond J Hohl, Hui Zeng, Hong Zheng
BACKGROUND: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28598382/syk-activity-is-dispensable-for-platelet-gp1b-ix-v-signaling
#8
Rachit Badolia, John C Kostyak, Carol Dangelmaier, Satya P Kunapuli
The binding of von Willebrand factor (VWF) to the platelet membrane glycoprotein 1b-IX (GP1b-IX) leads to activation of platelets. GP1b was shown to signal via the FcRγ-ITAM (Fc Receptor γ-Immunoreceptor tyrosine-based activation motif) pathway, activating spleen tyrosine kinase (Syk) and other tyrosine kinases. However, there have been conflicting reports regarding the role of Syk in GP1b signaling. In this study, we sought to resolve these conflicting reports and clarify the role of Syk in VWF-induced platelet activation...
June 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28526413/tcr-crosslinking-promotes-crk-adaptor-protein-binding-to-tyrosine-phosphorylated-cd3%C3%AE-chain
#9
Guangyu Dong, Rachel Kalifa, Pulak Ranjan Nath, Sigal Gelkop, Noah Isakov
T cell antigen receptor (TCR) binding of a peptide antigen presented by antigen-presenting cells (APCs) in the context of surface MHC molecules initiates signaling events that regulate T cell activation, proliferation and differentiation. A key event in the activation process is the phosphorylation of the conserved tyrosine residues within the CD3 chain immunoreceptor tyrosine-based activation motifs (ITAMs), which operate as docking sites for SH2 domain-containing effector proteins. Phosphorylation of the CD3ζ ITAMs renders the CD3 chain capable of binding the ζ-chain associated protein 70 kDa (ZAP70), a protein tyrosine kinase that is essential for T cell activation...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28515726/comparative-analysis-of-immune-checkpoint-molecules-and-their-potential-role-in-the-transmissible-tasmanian-devil-facial-tumor-disease
#10
Andrew S Flies, Nicholas B Blackburn, Alan Bruce Lyons, John D Hayball, Gregory M Woods
Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28511131/genetic-diversity-and-phylogenetic-analysis-of-the-orf5-gene-of-prrsv-from-central-china
#11
Liujun Zhang, Yan Feng, Darren P Martin, Jing Chen, Sixu Ma, Pingan Xia, Gaiping Zhang
To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis. Phylogenetic analysis revealed that all Henan isolates belonged to the Type 2 genotype and could be further divided into three subgroups. Subgroup 1 and 2 viruses predominated in Henan and subgroup 2 overtook subgroup 1 as the most prevalent PRRSV between 2006 and 2015...
May 11, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28498033/development-and-characterization-of-novel-monoclonal-antibodies-against-human-dnam-1
#12
Genki Okumura, Fumie Abe, Rei Hirochika, Akira Shibuya, Kazuko Shibuya
DNAM-1 (CD226) is an activating immunoreceptor expressed on lymphocytes and myeloid cells. CD155 and CD112 are the ligands for DNAM-1. DNAM-1 plays an important role in tumor immunity mediated by CD8(+) T cells and NK cells. Moreover, the interaction of DNAM-1 with the ligands contributed to the development of acute graft versus host disease (GVHD) and treatment with anti-DNAM-1 monoclonal antibodies (mAb) dramatically improved acute GVHD in a mouse model, suggesting that DNAM-1 may be a good molecular target for therapy to acute GVHD in human...
June 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28468914/rig-i-resists-hypoxia-induced-immunosuppression-and-dedifferentiation
#13
Christina Engel, Grethe Brügmann, Silke Lambing, Larissa H Mühlenbeck, Samira Marx, Christian Hagen, Dorottya Horváth, Marion Goldeck, Janos Ludwig, Anna-Maria Herzner, Jan W Drijfhout, Daniela Wenzel, Christoph Coch, Thomas Tüting, Martin Schlee, Veit Hornung, Gunther Hartmann, Jasper G Van den Boorn
A hypoxic tumor microenvironment is linked to poor prognosis. It promotes tumor cell dedifferentiation and metastasis and desensitizes tumor cells to type-I IFN, chemotherapy, and irradiation. The cytoplasmic immunoreceptor retinoic acid-inducible gene-I (RIG-I) is ubiquitously expressed in tumor cells and upon activation by 5'-triphosphate RNA (3pRNA) drives the induction of type I IFN and immunogenic cell death. Here, we analyzed the impact of hypoxia on the expression of RIG-I in various human and murine tumor and nonmalignant cell types and further investigated its function in hypoxic murine melanoma...
June 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28466386/current-status-and-perspectives-of-chimeric-antigen-receptor-modified-t-cells-for-cancer-treatment
#14
REVIEW
Zhenguang Wang, Yelei Guo, Weidong Han
Chimeric antigen receptor (CAR) is a recombinant immunoreceptor combining an antibody-derived targeting fragment with signaling domains capable of activating cells, which endows T cells with the ability to recognize tumor-associated surface antigens independent of the expression of major histocompatibility complex (MHC) molecules. Recent early-phase clinical trials of CAR-modified T (CAR-T) cells for relapsed or refractory B cell malignancies have demonstrated promising results (that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia (B-ALL))...
May 2, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28465343/itim-receptors-more-than-just-inhibitors-of-platelet-activation
#15
Carmen H Coxon, Mitchell J Geer, Yotis A Senis
Since their discovery, immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptors have been shown to inhibit signaling from immunoreceptor tyrosine-based activation motif (ITAM)-containing receptors in almost all hematopoietic cells, including platelets. However, a growing body of evidence has emerged demonstrating that this is an over-simplification, and that ITIM-containing receptors are versatile regulators of platelet signal transduction, with functions beyond inhibiting ITAM-mediated platelet activation...
May 2, 2017: Blood
https://www.readbyqxmd.com/read/28440726/expression-of-c-type-lectin-receptor-mrna-in-chronic-otitis-media-with-cholesteatoma
#16
Sang Hoon Kim, Seung-Ho Han, Jae Yong Byun, Moon Suh Park, Young Il Kim, Seung Geun Yeo
CONCLUSIONS: The levels of expression of various C-type lectin receptors (CLRs) messenger ribo nucleic acids (mRNAs) were significantly higher in cholesteatomas than in normal skin, suggesting that these CLRs may be involved in the pathogenesis of cholesteatoma. OBJECTIVES: Altered expression of pattern recognition receptors may be associated with immune responses in patients with cholesteatoma. This study assessed the levels of expression of CLR mRNAs in normal skin and in cholesteatoma...
June 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28439271/cross-talk-between-inhibitory-immunoreceptor-tyrosine-based-activation-motif-signaling-and-toll-like-receptor-pathways-in-macrophages-and-dendritic-cells
#17
REVIEW
Ivan Hirsch, Vaclav Janovec, Ruzena Stranska, Nathalie Bendriss-Vermare
The innate immune cells sense microbial infection and self-ligands by pathogen recognition receptors (PRRs), such as toll-like receptors (TLRs) and regulatory receptors (RRs), associated with immunoreceptor tyrosine-based activation motif (ITAM). Rapid activation and concerted action of PRRs signaling and feedback inhibitory mechanisms must be engaged to ensure the host defense functions and to prevent cytotoxicity associated with excessive activation. ITAM-associated RRs can generate stimulatory or, paradoxically, inhibitory signals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28424516/slamf7-is-critical-for-phagocytosis-of-haematopoietic-tumour-cells-via-mac-1-integrin
#18
Jun Chen, Ming-Chao Zhong, Huaijian Guo, Dominique Davidson, Sabrin Mishel, Yan Lu, Inmoo Rhee, Luis-Alberto Pérez-Quintero, Shaohua Zhang, Mario-Ernesto Cruz-Munoz, Ning Wu, Donald C Vinh, Meenal Sinha, Virginie Calderon, Clifford A Lowell, Jayne S Danska, André Veillette
Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo, suggesting that blockade of the SIRPα-CD47 checkpoint could be useful in treating human cancer...
April 27, 2017: Nature
https://www.readbyqxmd.com/read/28416139/cars-synthetic-immunoreceptors-for-cancer-therapy-and-beyond
#19
REVIEW
ZeNan L Chang, Yvonne Y Chen
Chimeric antigen receptors (CARs) are versatile synthetic receptors that provide T cells with engineered specificity. Clinical success in treating B-cell malignancies has demonstrated the therapeutic potential of CAR-T cells against cancer, and efforts are underway to expand the use of engineered T cells to the treatment of diverse medical conditions, including infections and autoimmune diseases. Here, we review current understanding of the molecular properties of CARs, how this knowledge informs the rational design and characterization of novel receptors, the successes and shortcomings of CAR-T cells in the clinic, and emerging solutions for the continued improvement of CAR-T cell therapy...
May 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28414292/dendritic-cells-expressing-immunoreceptor-cd300f-are-critical-for-controlling-chronic-gut-inflammation
#20
Ha-Na Lee, Linjie Tian, Nicolas Bouladoux, Jacquice Davis, Mariam Quinones, Yasmine Belkaid, John E Coligan, Konrad Krzewski
Proinflammatory cytokine overproduction and excessive cell death, coupled with impaired clearance of apoptotic cells, have been implicated as causes of failure to resolve gut inflammation in inflammatory bowel diseases. Here we have found that dendritic cells expressing the apoptotic cell-recognizing receptor CD300f play a crucial role in regulating gut inflammatory responses in a murine model of colonic inflammation. CD300f-deficient mice failed to resolve dextran sulfate sodium-induced colonic inflammation as a result of defects in dendritic cell function that were associated with abnormal accumulation of apoptotic cells in the gut...
May 1, 2017: Journal of Clinical Investigation
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