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https://www.readbyqxmd.com/read/28543380/chimeric-antigen-receptor-modified-t-cells-that-target-chemokine-receptor-ccr4-as-a-therapeutic-modality-for-t-cell-malignancies
#1
Liyanage P Perera, Meili Zhang, Masao Nakagawa, Michael N Petrus, Michiyuki Maeda, Marshall E Kadin, Thomas A Waldmann, Pin-Yu Perera
No abstract text is available yet for this article.
May 20, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28536288/cnot4-mediated-ubiquitination-of-influenza-a-virus-nucleoprotein-promotes-viral-rna-replication
#2
Yu-Chen Lin, King-Song Jeng, Michael M C Lai
Influenza A virus (IAV) RNA segments are individually packaged with viral nucleoprotein (NP) and RNA polymerases to form a viral ribonucleoprotein (vRNP) complex. We previously reported that NP is a monoubiquitinated protein which can be deubiquitinated by a cellular ubiquitin protease, USP11. In this study, we identified an E3 ubiquitin ligase, CNOT4 (Ccr4-Not transcription complex subunit 4), which can ubiquitinate NP. We found that the levels of viral RNA, protein, viral particles, and RNA polymerase activity in CNOT4 knockdown cells were lower than those in the control cells upon IAV infection...
May 23, 2017: MBio
https://www.readbyqxmd.com/read/28526296/mesenchymal-stem-cells-mscs-attenuate-cutaneous-sclerodermatous-graft-versus-host-disease-scl-gvhd-through-inhibition-of-immune-cell-infiltration-in-a-mouse-model
#3
Ji-Young Lim, Da-Bin Ryu, Sung-Eun Lee, Gyeongsin Park, Chang-Ki Min
Human chronic graft-versus-host disease (CGVHD) shares clinical characteristics with a murine sclerodermatous GVHD (Scl-GVHD) model that is characterized by skin thickening and lung fibrosis. A B10.D2 → BALB/c transplant model of Scl-GVHD was used to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of CGVHD. The clinical and pathological severity of cutaneous Scl-GVHD was significantly attenuated in MSC-treated recipients relative to Scl-GVHD controls. After MSC treatment, skin collagen production was significantly reduced with consistent downregulation of TGF-β expression...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28487484/cap-binding-protein-4ehp-effects-translation-silencing-by-micrornas
#4
Clément Chapat, Seyed Mehdi Jafarnejad, Edna Matta-Camacho, Geoffrey G Hesketh, Idit A Gelbart, Jan Attig, Christos G Gkogkas, Tommy Alain, Noam Stern-Ginossar, Marc R Fabian, Anne-Claude Gingras, Thomas F Duchaine, Nahum Sonenberg
MicroRNAs (miRNAs) play critical roles in a broad variety of biological processes by inhibiting translation initiation and by destabilizing target mRNAs. The CCR4-NOT complex effects miRNA-mediated silencing, at least in part through interactions with 4E-T (eIF4E transporter) protein, but the precise mechanism is unknown. Here we show that the cap-binding eIF4E-homologous protein 4EHP is an integral component of the miRNA-mediated silencing machinery. We demonstrate that the cap-binding activity of 4EHP contributes to the translational silencing by miRNAs through the CCR4-NOT complex...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28487109/ccr4-mediated-chemotaxis-of-regulatory-t-cells-suppress-the-activation-of-t-cells-and-nk-cells-via-tgf-%C3%AE-pathway-in-human-non-small-cell-lung-cancer
#5
Wei Liu, Xinyi Wei, Lin Li, Xiaobin Wu, Junli Yan, Hui Yang, Fangzhou Song
C-C chemokine receptor type 4 has been reported to correlate with lung cancer. However, the role of CCR4 in human non-small cell lung cancer patients is not well defined. Here, we demonstrated that increased expression of CCR4 was associated with clinical stage and CCR4 was an independent risk factor for overall survival in NSCLC patients. Moreover, tumor-infiltrating Treg cells were higher expression than matched adjacent tissues in CCR4+ NSCLC. Higher expression of chemokine CCL17 and CCL22 could recruit Treg cells to tumor sites in NSCLC...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28484158/adult-t-cell-leukemia-lymphoma-complicated-by-takotsubo-cardiomyopathy-and-htlv-1-associated-myelopathy-after-treatment-with-the-anti-ccr4-antibody-mogamulizumab
#6
Satoshi Yamanaka, Kazutaka Nakayama, Hayato Tamai, Masanori Sakamaki, Koiti Inokuchi
Adult T-cell leukemia-lymphoma (ATL) caused by human T-lymphotropic virus type 1 (HTLV-1) is generally associated with poor prognosis. The anti-CCR4 antibody mogamulizumab is one of the options for refractory or relapsed ATL. Mogamulizumab is intravenously administered as a single agent at a dose of 1.0 mg/kg once a week for 8 weeks. The overall response rate is reported to be 50%. Reported common adverse events after administration of mogamulizumab are leukocytopenia, infusion reaction, and skin rash. Although rare, mogamulizumab-associated cardiomyopathy has also been reported...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28482037/a-non-canonical-site-reveals-the-cooperative-mechanisms-of-microrna-mediated-silencing
#7
Mathieu N Flamand, Hin Hark Gan, Vinay K Mayya, Kristin C Gunsalus, Thomas F Duchaine
Although strong evidence supports the importance of their cooperative interactions, microRNA (miRNA)-binding sites are still largely investigated as functionally independent regulatory units. Here, a survey of alternative 3΄UTR isoforms implicates a non-canonical seedless site in cooperative miRNA-mediated silencing. While required for target mRNA deadenylation and silencing, this site is not sufficient on its own to physically recruit miRISC. Instead, it relies on facilitating interactions with a nearby canonical seed-pairing site to recruit the Argonaute complexes...
May 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28481655/young-adult-binge-drinkers-have-immunophenotypic-changes-in-peripheral-polymorphonuclear-cells-and-monocytes
#8
Adolfo Pérez-García, América Guadalupe Arroyo-Valerio, José Luis Zaldivar-Fujigaki, Mayra A Bustos-Esquivel, Alfonso Gastelum-Strozzi, Miguel A Padilla-Castañeda, Arturo Reding-Bernal, David Kershenobich, Joselín Hernández-Ruiz
BACKGROUND: High alcohol intake on weekends (binge drinking) is more frequent in young adults, who could undergo early liver damage. Alcohol-induced liver damage is characterized by polymorphonuclear cell (PMN) infiltration, which can be represented in the peripheral blood by altered trafficking and activation profiles. OBJECTIVE: To evaluate the PMN trafficking and activation immunophenotypic profiles in people with a binge drinking pattern. METHODS: People with binge drinking (n = 18, 8 females) or at low risk (n = 16, 13 females) based on their AUDIT and HEPCA scores were studied...
May 8, 2017: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28480561/immunotherapy-induced-sarcoidosis-in-patients-with-melanoma-treated-with-pd-1-checkpoint-inhibitors-case-series-and-immunophenotypic-analysis
#9
Anna J Lomax, Helen M McGuire, Catriona McNeil, Clara J Choi, Peter Hersey, Deme Karikios, Kerwin Shannon, Sebastian van Hal, Urszula Carr, Anne Crotty, Sandeep K Gupta, Jane Hollingsworth, Haewon Kim, Barbara Fazekas de St Groth, Neil McGill
AIM: Sarcoidosis is a multisystem granulomatous disease. This condition has a documented association with the diagnosis of melanoma and can be induced in melanoma patients receiving anti-neoplastic therapy. We evaluated a case series of melanoma patients who developed immunotherapy-induced sarcoidosis. METHODS: Three patients with melanoma (n = 1 resected Stage III, n = 2 metastatic) treated with anti-programmed cell death (PD)-1 antibody therapy at two institutions developed biopsy-proven sarcoidosis...
May 8, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28473716/cnot3-enhances-human-embryonic-cardiomyocyte-proliferation-by-promoting-cell-cycle-inhibitor-mrna-degradation
#10
Bingying Zhou, Junwei Liu, Zongna Ren, Fang Yao, Jingwei Ma, Jiangping Song, Brian Bennett, Yisong Zhen, Li Wang, Guang Hu, Shengshou Hu
Uncovering the molecular basis of mammalian cardiomyocyte proliferation may eventually lead to better approaches for heart regeneration. Compared to extensively-studied transcriptional regulation, the roles of posttranscriptional regulation in cardiac cell fate decisions remain largely unknown. Here, we identified Cnot3 as a critical regulator in cardiomyocyte proliferation at the late stage of cardiac differentiation from human ESCs. Cnot3 was highly expressed in cardiomyocytes with higher proliferation potential in both human and mouse, and its depletion resulted in significant reduction in the proliferative capacity of cells...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28466278/improving-antibody-based-cancer-therapeutics-through-glycan-engineering
#11
REVIEW
Xiaojie Yu, Michael J E Marshall, Mark S Cragg, Max Crispin
Antibody-based therapeutics has emerged as a major tool in cancer treatment. Guided by the superb specificity of the antibody variable domain, it allows the precise targeting of tumour markers. Recently, eliciting cellular effector functions, mediated by the Fc domain, has gained traction as a means by which to generate more potent antibody therapeutics. Extensive mutagenesis studies of the Fc protein backbone has enabled the generation of Fc variants that more optimally engage the Fcγ receptors known to mediate cellular effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and cellular phagocytosis...
May 2, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28421534/immune-alterations-in-cd8-t-cells-are-associated-with-neuronal-c-c-and-c-x-c-chemokine-receptor-regulation-through-adenosine-a2a-receptor-signaling-in-a-btbr-t-itpr3-tf-j-autistic-mouse-model
#12
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Raish Mohammad, Sabry M Attia
Associative studies on a range of neurodevelopmental disorders have identified relationships between behavioral deficits and immune system function. The BTBR T(+) Itpr3(tf)/J (BTBR) mouse strain displays aberrant characteristics in its social behavior and immune responses, providing a significant opportunity to examine the relationship between behavior and the immune system. This study investigated the influence of adenosine A2A receptor activity on C-C and C-X-C chemokine receptors involved in autism in the BTBR mouse model...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28415693/ccr4-is-a-determinant-of-melanoma-brain-metastasis
#13
Anat Klein, Orit Sagi-Assif, Tsipi Meshel, Alona Telerman, Sivan Izraely, Shlomit Ben-Menachem, Jagadeesh Bayry, Diego M Marzese, Shuichi Ohe, Dave S B Hoon, Neta Erez, Isaac P Witz
We previously identified the chemokine receptor CCR4 as part of the molecular signature of melanoma brain metastasis. The aim of this study was to determine the functional significance of CCR4 in melanoma brain metastasis. We show that CCR4 is more highly expressed by brain metastasizing melanoma cells than by local cutaneous cells from the same melanoma. Moreover, we found that the expression of CCR4 is significantly higher in paired clinical specimens of melanoma metastases than in samples of primary tumors from the same patients...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408751/mmp9-integrates-multiple-immunoregulatory-pathways-that-discriminate-high-suppressive-activity-of-human-mesenchymal-stem-cells
#14
Carolina Lavini-Ramos, Hernandez Moura Silva, Alessandra Soares-Schanoski, Sandra Maria Monteiro, Ludmila Rodrigues Pinto Ferreira, Ana Paula Pacanaro, Samirah Gomes, Janaína Batista, Kellen Faé, Jorge Kalil, Verônica Coelho
The mechanisms underlying mesenchymal stem cells' (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-γ and TNF-α production, along IL-10 increase, (ii) CD73(+)Foxp3(+)Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28404620/accumulation-of-rna-on-chromatin-disrupts-heterochromatic-silencing
#15
Cornelia Brönner, Luca Salvi, Manuel Zocco, Ilaria Ugolini, Mario Halic
Long non-coding RNAs (lncRNAs) play a conserved role in regulating gene expression, chromatin dynamics and cell differentiation. They serve as a platform for RNA interference (RNAi)-mediated heterochromatin formation or DNA methylation in many eukaryotic organisms. We found in Schizosaccharomyces pombe, that heterochromatin is lost at transcribed regions in absence of RNA degradation. We show that heterochromatic RNAs are retained on chromatin, form DNA:RNA hybrids and need to be degraded by the Ccr4-Not complex or RNAi to maintain heterochromatic silencing...
April 12, 2017: Genome Research
https://www.readbyqxmd.com/read/28392462/blood-to-skin-recirculation-of-cd4-memory-t-cells-associates-with-cutaneous-and-systemic-manifestations-of-psoriatic-disease
#16
Marco Diani, Marco Galasso, Chiara Cozzi, Francesco Sgambelluri, Andrea Altomare, Clara Cigni, Elena Frigerio, Lorenzo Drago, Stefano Volinia, Francesca Granucci, Gianfranco Altomare, Eva Reali
Blood to skin recirculation could play a role in the pathogenesis of psoriasis. To investigate this possibility we dissected the phenotype of circulating T cells in psoriasis patients, calculated the correlation the clinical parameters of the disease and performed a parallel bioinformatics analysis of gene expression data in psoriatic skin. We found that circulating CCR6(+) CD4(+) TEM and TEFF cells significantly correlated with systemic inflammation. Conversely, the percentage of CXCR3(+) CD4(+) TEM cells negatively correlated with the severity of the cutaneous disease...
April 6, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28389623/neoplastic-plasma-cells-generate-an-inflammatory-environment-within-bone-marrow-and-markedly-alter-the-distribution-of-t-cells-between-lymphoid-compartments
#17
Oliver C Goodyear, Sarah Essex, Anandram Seetharam, Supratik Basu, Paul Moss, Guy Pratt
Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) are characterised by the accumulation of malignant plasma cells within bone marrow and lead to a range of abnormalities in the peripheral blood T cell repertoire. We investigated the level of inflammatory chemokines within the bone marrow and blood of patients with MGUS and MM and related this to the pattern of chemokine receptor expression on T cells in both compartments.The expression of a wide range of chemokine ligands for CXCR3 and CCR4 was markedly increased within the bone marrow of patients with MGUS and MM compared to healthy donors...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387445/stimulation-of-oral-fibroblast-chemokine-receptors-identifies-ccr3-and-ccr4-as-potential-wound-healing-targets
#18
Jeroen K Buskermolen, Sanne Roffel, Susan Gibbs
The focus of this study was to determine which chemokine receptors are present on oral fibroblasts and whether these receptors influence proliferation, migration, and/or the release of wound healing mediators. This information may provide insight into the superior wound healing characteristics of the oral mucosa. The gingiva fibroblasts expressed 12 different chemokine receptors (CCR3, CCR4, CCR6, CCR9, CCR10, CXCR1, CXCR2, CXCR4, CXCR5, CXCR7, CX3CR1, and XCR1), as analyzed by flow cytometry. Fourteen corresponding chemokines (CCL5, CCL15, CCL20, CCL22, CCL25, CCL27, CCL28, CXCL1, CXCL8, CXCL11, CXCL12, CXCL13, CX3CL1, and XCL1) were used to study the activation of these receptors on gingiva fibroblasts...
April 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28385330/a-similar-local-immune-and-oxidative-stress-phenotype-in-vitiligo-and-halo-nevus
#19
Yuqi Yang, Shuli Li, Guannan Zhu, Qian Zhang, Gang Wang, Tianwen Gao, Chunying Li, Lin Wang, Zhe Jian
BACKGROUND: Vitiligo and halo nevus are two common T-cell-mediated skin disorders. Although autoimmunity has been suggested to be involved in both diseases, the relationship between vitiligo and halo nevus is not fully understood. OBJECTIVE: The aim of the current study was to investigate whether vitiligo and halo nevus share the same immunological and oxidative stress response. METHODS: Infiltrations of T cells, and expressions of chemokine receptors (CXCR3, CCR4, CCR5) and cytotoxic markers (Granzyme B, Perforin) in the lesions of vitiligo and halo nevus were examined by immunohistochemistry...
March 19, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28383711/synergistic-effect-of-regulatory-t-cells-and-proinflammatory-cytokines-in-angiogenesis-in-the-endometriotic-milieu
#20
Xiao-Qiu Wang, Wen-Jie Zhou, Xue-Zhen Luo, Yu Tao, Da-Jin Li
STUDY QUESTION: Do regulatory T cells (Tregs) contribute to angiogenesis in endometriosis? SUMMARY ANSWER: High levels of CCL17 and CCL22 cause the recruitment of Tregs, upregulate the immunosuppression of Tregs and, in turn, may promote angiogenesis in endometrial cells in synergy with proinflammatory cytokines. WHAT IS ALREADY KNOWN: The peritoneal fluid of patients with endometriosis has a higher percentage of Tregs than that of normal individuals; however, the regulatory role of Tregs in the disease remains unclear...
June 1, 2017: Human Reproduction
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