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https://www.readbyqxmd.com/read/29346571/natural-course-of-htlv-1-proviral-dna-levels-in-carriers-during-pregnancy
#1
Naoki Fuchi, Kiyonori Miura, Takashi Tsukiyama, Daisuke Sasaki, Kaori Ishihara, Kazuto Tsuruda, Hiroo Hasegawa, Shoko Miura, Katsumi Yanagihara, Hideaki Masuzaki
The measurement of human T-cell leukemia virus type 1 (HTLV-1) proviral DNA levels using polymerase chain reaction has been beneficial for confirming HTLV-1 infection during pregnancy. However, the influence of pregnancy on HTLV-1 infection and proviral DNA levels among pregnant women with HTLV-1 has not been clarified. We prospectively gathered blood samples from 36 pregnant women who were previously diagnosed as HTLV-1 carriers and sequentially measured their proviral DNA levels. The HTLV-1 proviral DNA levels remained in a plateau during pregnancy but were elevated after delivery...
January 16, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29346345/the-cytosolic-sensor-sting-is-required-for-intestinal-homeostasis-and-control-of-inflammation
#2
M C C Canesso, L Lemos, T C Neves, F M Marim, T B R Castro, É S Veloso, C P Queiroz, J Ahn, H C Santiago, F S Martins, J Alves-Silva, E Ferreira, D C Cara, A T Vieira, G N Barber, S C Oliveira, A M C Faria
STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING-/- mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346301/braf-and-mek-inhibitors-influence-the-function-of-reprogrammed-t-cells-consequences-for-adoptive-t-cell-therapy
#3
Jan Dörrie, Lek Babalija, Stefanie Hoyer, Kerstin F Gerer, Gerold Schuler, Lucie Heinzerling, Niels Schaft
BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with BRAFV600 mutated melanoma, are currently explored in combination with various immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor-transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are approved, potential differences in their effects on immune cells would enable a rational choice for triple therapies. Therefore, we characterized the influence of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and trametinib (Tram) vs...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29345922/efficient-fusion-at-neutral-ph-by-human-immunodeficiency-virus-gp41-trimers-containing-the-fusion-peptide-and-transmembrane-domain
#4
Shuang Liang, Punsisi Ratnayake, Craig Keinath, Lihui Jia, Robert Wolfe, Ahinsa Ranaweera, David P Weliky
Human immunodeficiency virus (HIV) is membrane-enveloped and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41 which is a single-pass integral viral membrane protein. The protein contains a ~170-residue ectodomain located outside the virus that is important for fusion, and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). The virion initially has non-covalent complexes between three gp41 ectodomains and three gp120 proteins...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29345621/the-circulating-t-helper-subsets-and-regulatory-t-cells-in-patients-with-common-variable-immunodeficiency-with-no-known-monogenic-disease
#5
G Azizi, A Mirshafiey, H Abolhassani, R Yazdani, F J Ansariha, M Shaghaghi, S S Mortazavi-Jahromi, F Noorbakhsh, N Rezaei, A Aghamohammadi
BACKGROUND: Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID), characterized by heterogeneous clinical manifestations and defects in B- and T- cells. In the present study, we investigated the T helper (Th) cell subsets and regulatory T (Treg) cells, and their related cytokines and transcription factors in the CVID patients with no definite genetic diagnosis. METHODS: The study population comprised 13 CVID patients and 13 healthy controls (HC)...
January 18, 2018: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/29345428/traf3-regulation-of-inhibitory-signaling-pathways-in-b-and-t-lymphocytes-by-kinase-and-phosphatase-localization
#6
REVIEW
Alicia M Wallis, Gail A Bishop
This brief review presents current understanding of how the signaling adapter protein TRAF3 can both induce and block inhibitory signaling pathways in B and T lymphocytes, via association with kinases and phosphatases, and subsequent regulation of their localization within the cell. In B lymphocytes, signaling through the interleukin 6 receptor (IL-6R) induces association of TRAF3 with IL-6R-associated JAK1, to which TRAF3 recruits the phosphatase PTPN22 (protein tyrosine phosphatase number 22) to dephosphorylate JAK1 and STAT3, inhibiting IL-6R signaling...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345372/truncation-of-neurokinin-1-receptor-negative-regulation-of-substance-p-signaling
#7
REVIEW
Sergei Spitsin, Vasiliki Pappa, Steven D Douglas
Substance P (SP) is a tachykinin peptide, which triggers intracellular signaling in the nervous and immune systems, as well as, other local and systemic events. The interaction between SP and its receptor, neurokinin-1 receptor (NK1R), results in major downstream cellular actions, which include changes in calcium fluxes, ERK, and p21-activated kinase phosphorylation and NFκB activation. Two naturally occurring variants of the NK1R, the full-length, 407 aa receptor (NK1R-F) and the truncated, 311 aa isoform (NK1R-T), mediate the actions of SP...
January 10, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345363/effects-of-il-10-and-th-2-cytokines-on-human-m%C3%AF-phenotype-and-response-to-csf1r-inhibitor
#8
Leon P Pradel, Andreas Franke, Carola H Ries
Tumor-associated Mφs display a plastic phenotype that is regulated by the local tumor milieu. Gene expression analysis and functional characterization of Mφs exposed in vitro to individual cytokines aids to delineate the cross-talk between defined cytokines shaping the complex Mφ phenotype. Human monocyte-derived Mφs can be differentiated in vitro with the T helper cell type 2 response cytokines IL-4 and IL-13 or the immunosuppressive IL-10. Notably, only the latter subset undergoes apoptosis when treated with the CSF 1 receptor (CSF1R) blocking antibody emactuzumab...
January 4, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345065/fingolimod-targets-cerebral-endothelial-activation-to-block-leukocyte-recruitment-in-the-central-nervous-system
#9
Yawei Zhao, Dongyan Shi, Kelei Cao, Fengjiao Wu, Xingxing Zhu, Shuang Wen, Qiang You, Keqi Zhang, Lixin Liu, Hong Zhou
Fingolimod (FTY720), an immunomodulator, is approved as an oral treatment for patients with relapsing forms of multiple sclerosis. Its effects are largely attributed to its mechanism of selectively retaining lymphocytes in the lymph nodes to reduce autoreactive T-cell recruitment in the CNS. In this study, we investigated the therapeutic effect of FTY720 on an animal model of CNS inflammation induced by intracerebral ventricle LPS injection. We found that FTY720 treatment significantly prevented LPS-induced neutrophil recruitment in the CNS by inhibiting leukocyte recruitment in cerebral microvessels...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345058/frontline-science-anti-pd-l1-protects-against-infection-with-common-bacterial-pathogens-after-burn-injury
#10
Naeem K Patil, Liming Luan, Julia K Bohannon, Antonio Hernandez, Yin Guo, Edward R Sherwood
Burn patients are susceptible to infections due, in part, to immune dysfunction. Upregulation of programmed death-1 (PD-1) receptor on T cells and programmed cell death ligand-1 (PD-L1) on myeloid cells contribute to immune dysfunction in nonburn-related sepsis. We hypothesized that PD-1/PDL1 interactions contribute to immune dysfunction after burn injury. To determine the impact of burn injury and infection on PD-L1, PD-1 and costimulatory receptor expression by leukocytes and its relationship to T cell functions...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344676/application-of-genome-editing-techniques-in-immunology
#11
REVIEW
Agata O Zych, Malgorzata Bajor, Radoslaw Zagozdzon
The idea of using the effector immune cells to specifically fight cancer has recently evolved into an exciting concept of adoptive cell therapies. Indeed, genetically engineered T cells expressing on their surface recombinant, cancer-targeted receptors have been shown to induce promising response in oncological patients. However, in addition to exogenous expression of such receptors, there is also a need for disruption of certain genes in the immune cells to achieve more potent disease-targeted actions, to produce universal chimeric antigen receptor-based therapies or to study the signaling pathways in detail...
January 17, 2018: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29344645/targeted-disruption-of-adenosine-kinase-in-myeloid-monocyte-cells-increases-osteoclastogenesis-and-bone-resorption-in-mice
#12
Qiuying Ye, Ge Li, Shuhua Liu, Yalun Guan, Yunfeng Li, Jinling Li, Huanhuan Jia, Xuejiao Li, Qingnan Li, Ren Huang, Hui Wang, Yu Zhang
Adenosine kinase (ADK) serves an important role in intracellular adenosine clearance via phosphorylating adenosine to AMP. The role of adenosine and its receptors in the maintenance of bone homeostasis is well studied, particularly in osteoclastogenesis and bone resorption; however, the function of ADK in bone metabolism is still unclear. In the present study, utilizing the cre/floxp recombination system, mice with conditional loss of ADK function in myeloid monocyte cells were used to assess the effect of ADK deficiency on bone metabolism...
January 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29344586/systemic-multilineage-engraftment-in-mice-after-in-utero-transplantation-with-human-hematopoietic-stem-cells
#13
Russell G Witt, Emily M Kreger, Laura B Buckman, Patriss W Moradi, Phong T Ho, S Christopher Derderian, Perry Tsai, Chris Baker, Nathaniel Schramm, Rachel Cleary, J Victor Garcia, Tippi C MacKenzie
IUHCT of human cord blood-derived CD34+ cells into fetal NSG mice results in systemic multilineage engraftment with human cells.Preconditioning with in utero injection of an anti-c-Kit receptor antibody (ACK2) results in an improved rate of engraftment.
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29344217/aleukemic-extramedullary-t-lymphoid-myeloid-bilineage-hematopoietic-and-lymphoid-malignancy-with-progression-to-bilineage-leukemia-at-relapse-a-case-report
#14
Mengyao Wu, Xiaoqiu Li, Feng Tang, Ping Zhu, Tianling Ding, Yan Yuan, Tong Chen
Bilineage T lymphoid and myeloid (T/My) neoplasms are rare entities among the hematopoietic and lymphoid malignancies. The majority of patients present with leukemic symptoms in which blasts are observed in the peripheral blood (PB) or bone marrow (BM) at a percentage of >20% of nucleated cells. Only a minimal number of cases of T/My bilineage hematopoietic and lymphoid malignancy have been reported with extramedullary infiltration as the initial symptom. The origin of the neoplastic cells in T/My bilineage malignancy has been documented as the hematopoietic stem cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344132/aberrant-nlrp3-inflammasome-associated-with-aryl-hydrocarbon-receptor-potentially-contributes-to-the-imbalance-of-t-helper-cells-in-patients-with-acute-myeloid-leukemia
#15
Yan Jia, Chen Zhang, Mingqiang Hua, Min Wang, Ping Chen, Daoxin Ma
Acute myeloid leukemia (AML) is a hematological malignancy in which the immune response serves a pivotal role in progression. Aryl hydrocarbon receptor (AHR) is involved in the modulation of the immune system, particularly in the differentiation of T-helper cell (Th) subsets. Although the NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been implicated as essential in the pathogenesis of autoimmune and inflammatory diseases, the role it serves in the development of AML remains unknown. Therefore, in order to identify and describe the possible roles of AHR, as well as NLRP3 inflammasome, in the pathogenesis of AML and their relationship with Th subsets (Th1 Th22), the present study investigated the mRNA expression levels of AHR and NLRP3 inflammasome molecules in the peripheral blood and bone marrow...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344085/synthesis-secretion-function-metabolism-and-application-of-natriuretic-peptides-in-heart-failure
#16
REVIEW
Shihui Fu, Ping Ping, Fengqi Wang, Leiming Luo
As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2...
2018: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29343807/house-dust-mite-induced-allergic-airway-disease-is-attenuated-in-cd11ccreil-4r%C3%AE-l%C3%A2-x-mice
#17
Natalie Eva Nieuwenhuizen, Frank Kirstein, Jennifer Claire Hoving, Frank Brombacher
The precise mechanisms leading to development of T helper type (Th)2-driven allergic responses are unknown. We aimed to determine how IL-4 receptor alpha (IL-4Rα) signaling on CD11c+ cells influences allergen-induced Th2 responses in mice. CD11ccreIL-4Rα-/l°x mice, deficient in IL-4Rα on dendritic cells and alveolar macrophages, were compared to IL-4Rα-/l°x littermate controls in models of allergic airway disease induced by OVA/alum, OVA alone or house dust mite. Cytokine responses, eosinophil and neutrophil infiltration into the lungs, airway hyperreactivity and mucus hypersecretion were evaluated after allergen challenge...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343689/a-novel-%C3%AE-conopeptide-eu1-6-inhibits-n-type-cav2-2-calcium-channels-and-exhibits-potent-analgesic-activity
#18
Zhuguo Liu, Peter Bartels, Mahsa Sadeghi, Tianpeng Du, Qing Dai, Cui Zhu, Shuo Yu, Shuo Wang, Mingxin Dong, Ting Sun, Jiabin Guo, Shuangqing Peng, Ling Jiang, David J Adams, Qiuyun Dai
We here describe a novel α-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong anti-nociceptive activity by an unexpected mechanism of action. Unlike other α-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the α3β4 and α7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343684/mait-cell-clonal-expansion-and-tcr-repertoire-shaping-in-human-volunteers-challenged-with-salmonella-paratyphi%C3%A2-a
#19
Lauren J Howson, Giorgio Napolitani, Dawn Shepherd, Hemza Ghadbane, Prathiba Kurupati, Lorena Preciado-Llanes, Margarida Rei, Hazel C Dobinson, Malick M Gibani, Karen Wei Weng Teng, Evan W Newell, Natacha Veerapen, Gurdyal S Besra, Andrew J Pollard, Vincenzo Cerundolo
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can detect bacteria-derived metabolites presented on MR1. Here we show, using a controlled infection of humans with live Salmonella enterica serovar Paratyphi A, that MAIT cells are activated during infection, an effect maintained even after antibiotic treatment. At the peak of infection MAIT cell T-cell receptor (TCR)β clonotypes that are over-represented prior to infection transiently contract. Select MAIT cell TCRβ clonotypes that expand after infection have stronger TCR-dependent activation than do contracted clonotypes...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343642/mechanogenetics-for-the-remote-and-noninvasive-control-of-cancer-immunotherapy
#20
Yijia Pan, Sangpil Yoon, Jie Sun, Ziliang Huang, Changyang Lee, Molly Allen, Yiqian Wu, Ya-Ju Chang, Michel Sadelain, K Kirk Shung, Shu Chien, Yingxiao Wang
While cell-based immunotherapy, especially chimeric antigen receptor (CAR)-expressing T cells, is becoming a paradigm-shifting therapeutic approach for cancer treatment, there is a lack of general methods to remotely and noninvasively regulate genetics in live mammalian cells and animals for cancer immunotherapy within confined local tissue space. To address this limitation, we have identified a mechanically sensitive Piezo1 ion channel (mechanosensor) that is activatable by ultrasound stimulation and integrated it with engineered genetic circuits (genetic transducer) in live HEK293T cells to convert the ultrasound-activated Piezo1 into transcriptional activities...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
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