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https://www.readbyqxmd.com/read/28817635/contractile-actomyosin-arcs-promote-the-activation-of-primary-mouse-t-cells-in-a-ligand-dependent-manner
#1
Jinsung Hong, Sricharan Murugesan, Eric Betzig, John A Hammer
Mechano-transduction is an emerging but still poorly understood component of T cell activation. Here we investigated the ligand-dependent contribution made by contractile actomyosin arcs populating the peripheral supramolecular activation cluster (pSMAC) region of the immunological synapse (IS) to T cell receptor (TCR) microcluster transport and proximal signaling in primary mouse T cells. Using super resolution microscopy, OT1-CD8+ mouse T cells, and two ovalbumin (OVA) peptides with different affinities for the TCR, we show that the generation of organized actomyosin arcs depends on ligand potency and the ability of myosin 2 to contract actin filaments...
2017: PloS One
https://www.readbyqxmd.com/read/28816296/-complete-androgen-insensitivity-syndrome-associated-with-vesical-fistula-a-case-report-and-literature-review
#2
K H Hua, L Yang, X W Zhang, W J Bai, Q Li, T Xu
Androgen insensitivity syndrome (AIS) is a very uncommon genetic disorder that results from the resistance of androgen receptor (AR) to androgen, which influences the formation of the male genitalia and in turn presents with female phenotype. Surgical resection of undesceaded testicle and different kinds of genitoplasty are crucial methods to correct the deformity of reproductive system, as well as hormone replacement therapy, which is an essential therapy for postoperational rehabilitation in AIS patients...
August 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28815581/th1-polarizing-%C3%AE-%C3%AE-t-cells-and-scavenger-receptors-contribute-to-the-pathogenesis-of-pemphigus-vulgaris
#3
Dayasagar Das, Vivek Anand, Sujay Khandpur, V K Sharma, Alpana Sharma
Gamma delta T cells (γδ T cells) and Scavenger receptors are key innate immune machinery playing significant role in regulating immune homeostasis at epithelial surface. The roles of these immune components are not yet characterized for the autoimmune skin disorder Pemphigus Vulgaris (PV). Phenotyping and frequency of γδ T cells estimated by Flowcytometry has shown increased frequency of γδ T cells (6.7% vs. 4.4%) producing IFN-γ (35.2% vs. 26.68%), in circulation of patients compared to controls. Dual cytokine (IFN-γ & IL-4) secreting γδ T cells indicate plasticity of these cells...
August 16, 2017: Immunology
https://www.readbyqxmd.com/read/28815225/chronic-in-vivo-interaction-of-dendritic-cells-expressing-the-ligand-rae-1%C3%AE%C2%B5-with-nk-cells-impacts-nkg2d-expression-and-function
#4
Maelig G Morvan, Marine Champsaur, Boris Reizis, Lewis L Lanier
To investigate how dendritic cells (DCs) interact with NK cells in vivo, we developed a novel mouse model in which Rae-1ε, a ligand of the NKG2D receptor, is expressed in cells with high levels of CD11c. In these CD11c-Rae1 mice, expression of Rae-1 was confirmed on all subsets of DCs and a small subset of B and T cells, but not on NK cells. DC numbers and activation status were unchanged, and NK cells in these CD11c-Rae1 mice presented the same Ly49 repertoire and maturation levels as their littermate wildtype controls...
May 1, 2017: Immunohorizons
https://www.readbyqxmd.com/read/28815044/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#5
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28814669/neonatal-and-adult-recent-thymic-emigrants-produce-il-8-and-express-complement-receptors-cr1-and-cr2
#6
Marcin L Pekalski, Arcadio Rubio García, Ricardo C Ferreira, Daniel B Rainbow, Deborah J Smyth, Meghavi Mashar, Jane Brady, Natalia Savinykh, Xaquin Castro Dopico, Sumiyya Mahmood, Simon Duley, Helen E Stevens, Neil M Walker, Antony J Cutler, Frank Waldron-Lynch, David B Dunger, Claire Shannon-Lowe, Alasdair J Coles, Joanne L Jones, Chris Wallace, John A Todd, Linda S Wicker
The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+CD25- naive T cells as defined by their levels of signal joint T cell receptor rearrangement excision circles (sjTRECs). Here, by differential gene expression analysis followed by protein expression and functional studies, we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814613/osteoimmunology-the-conceptual-framework-unifying-the-immune-and-skeletal-systems
#7
REVIEW
Kazuo Okamoto, Tomoki Nakashima, Masahiro Shinohara, Takako Negishi-Koga, Noriko Komatsu, Asuka Terashima, Shinichiro Sawa, Takeshi Nitta, Hiroshi Takayanagi
The immune and skeletal systems share a variety of molecules, including cytokines, chemokines, hormones, receptors, and transcription factors. Bone cells interact with immune cells under physiological and pathological conditions. Osteoimmunology was created as a new interdisciplinary field in large part to highlight the shared molecules and reciprocal interactions between the two systems in both heath and disease. Receptor activator of NF-κB ligand (RANKL) plays an essential role not only in the development of immune organs and bones, but also in autoimmune diseases affecting bone, thus effectively comprising the molecule that links the two systems...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28814173/early-diagnosis-of-severe-combined-immunodeficiency-scid-in-turkey-a-pilot-study
#8
Ceren Can, Şahin Hamilçıkan, Emrah Can
OBJECTIVE: Severe combined immunodeficiency (SCID) is a neonatal emergency. As the T cell receptor excision circles (TREC) test is not cost effective for neonatal screening of SCID in developing countries, this pilot study's objective aimed at identifying preliminary data to enable SCID identification in the general population. METHODS: This observational study was performed in Bagcılar Training and Research Hospital, Istanbul, Turkey. Cord-blood complete blood count (CBC) was recorded in all neonates included in the study...
August 17, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28814080/drug-delivery-from-a-multi-faceted-ultrasound-contrast-agent-influence-of-shell-composition
#9
Lauren J Jablonowski, Nutte T Teraphongphom, Margaret A Wheatley
Many cancer therapy regimes still rely heavily on the systemic administration of toxic chemotherapeutic agents. Ultrasound contrast agents consisting of microbubbles (MB) have emerged as a drug delivery vehicle to overcome the challenges associated with systemic chemotherapy. Here we describe the development of non-immunogenic, functionalized polylactic acid (PLA) MB for use in targeted cancer therapy. Our previous studies have shown that the balance between acoustic behavior and improved immune avoidance was scalable and successful to different degrees with two different PEGylation methods, and was best achieved using incorporation of PEG-PLA at 5 wt% and for a LipidPEG at 1 wt%...
August 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28814066/mice-expressing-human-erap1-variants-associated-with-ankylosing-spondylitis-have-altered-t-cell-repertoires-and-nk-cell-functions-as-well-as-increased-in-utero-and-perinatal-mortality
#10
David P W Rastall, Fadel S Alyaquob, Patrick O'Connell, Yuliya Pepelyayeva, Douglas Peters, Sarah Godbehere-Roosa, Cristiane Pereira-Hicks, Yasser A Aldhamen, Andrea Amalfitano
Specific variants of endoplasmic reticulum-associated aminopeptidase 1 (ERAP1) identified by genome-wide association study modify the risk for developing ankylosing spondylitis. We previously confirmed that disease-associated ERAP1 variants have altered enzymatic abilities that can impact upon the production of pro-inflammatory cytokines from cells expressing the same ERAP1 variants. To determine if these ERAP1 variants also impacted immune responses in vivo, we generated two strains of transgenic mice expressing human ERAP1 genes containing non-synonymous single-nucleotide polymorphisms associated with an increased (ERAP1-High) or decreased (ERAP1-Low) risk for developing autoimmune disease...
June 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28813656/fc%C3%AE-receptor-function-and-the-design-of-vaccination-strategies
#11
REVIEW
Stylianos Bournazos, Jeffrey V Ravetch
Through specific interactions with distinct types of Fcγ receptors (FcγRs), the Fc domain of immunoglobulin G (IgG) mediates a wide spectrum of immunological functions that influence both innate and adaptive responses. Recent studies indicate that IgG Fc-FcγR interactions are dynamically regulated during an immune response through the control of the Fc-associated glycan structure and Ig subclass composition on the one hand and selective FcγR expression on immune cells on the other, which together determine the capacity of IgG to interact in a cell-type-specific manner with specific members of the FcγR family...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28813640/innate-immune-signaling-in-the-ventral-tegmental-area-contributes-to-drug-primed-reinstatement-of-cocaine-seeking
#12
Kyle T Brown, Sophia C Levis, Casey E O'Neill, Alexis L Northcutt, Timothy J Fabisiak, Linda R Watkins, Ryan K Bachtell
Cocaine addiction is a chronic relapsing disorder characterized by persistent perturbations to an organism's homeostatic processes that result in maladaptive drug seeking. Although considerable attention has been directed at the consequences of neuronal changes following chronic cocaine taking, few studies have examined the role of microglia, the brain's resident immune cells, following chronic cocaine administration. Toll-Like Receptor 4 (TLR4) is a molecular pattern receptor that recognizes pathogens, danger signals, and xenobiotics and induces proinflammatory signaling in the central nervous system...
August 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28813462/a-comprehensive-profiling-of-t-and-b-lymphocyte-receptor-repertoires-from-a-chinese-origin-rhesus-macaque-by-high-throughput-sequencing
#13
Longfei Fu, Xinyang Li, Wei Zhang, Changxi Wang, Jinghua Wu, Huanming Yang, Jian Wang, Xiao Liu
Due to the close genetic background, high similarity of physiology, and susceptibility to infectious and metabolic diseases with humans, rhesus macaques have been widely used as an important animal model in biomedical research, especially in the study of vaccine development and human immune-related diseases. In recent years, high-throughput sequencing based immune repertoire sequencing (IR-SEQ) has become a powerful tool to study the dynamic adaptive immune responses. Several previous studies had analyzed the responses of B cells to HIV-1 trimer vaccine or T cell repertoire of rhesus macaques using this technique, however, there are little studies that had performed a comprehensive analysis of immune repertoire of rhesus macaques, including T and B lymphocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28812990/human-leukocyte-antigen-c-12-02-02-and-killer-immunoglobulin-like-receptor-2dl5-are-distinctly-associated-with-ankylosing-spondylitis-in-the-taiwanese
#14
Chin-Man Wang, Sheng-Hung Wang, Yeong-Jian Jan Wu, Jing-Chi Lin, Jianming Wu, Ji-Yih Chen
Human leukocyte antigen (HLA) class I ligands and Killer immunoglobulin-like receptors (KIRs) regulate the cytolytic activity of natural killer (NK) cells and certain T cells. We examined their genetic predisposition to disease susceptibility and clinical phenotypes in Taiwanese ankylosing spondylitis (AS) patients. KIR genotyping and Human Leucocyte Antigen C (HLA-C) sequencing were performed in 653 Taiwanese AS patients and 952 healthy controls. KIR genotype distributions and HLA-C allele frequencies were compared in patients and controls and among patients with and without HLA-B27 positivity, early age onset and spinal syndesmophytes...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-down-regulation-enhances-the-immunotherapy-response-of-nsclc-cells
#15
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of Class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28812183/anti-dll4-antibody-inhibits-the-differentiation-of-th17-cells-in-asthmatic-mice
#16
Cuiye Weng, Lei Chong, Xiaoxiao Jia, Rongying Zheng, Yue Huang, Tingting Zhu, Changchong Li, Weixi Zhang
T helper 17 (Th17) cells play an important role in allergic asthma, and the Notch ligand Delta-like ligand (Dll)4 has been reported to direct the differentiation of Th17 cells. In this study, experimental animals were divided into five groups (control group, asthma group, physiological saline group, anti-Dll4 antibody group, and immunoglobulin G group). The study aimed to explore the effect of anti-Dll4 antibody on the differentiation of Th17 cell in asthmatic mice. Dll4 protein expressions were performed by immunohistochemical imaging...
August 15, 2017: Inflammation
https://www.readbyqxmd.com/read/28812045/soluble-st2-predicts-outcome-and-hemorrhagic-transformation-after-acute-stroke
#17
Zoe Wolcott, Ayush Batra, Matthew B Bevers, Cristina Sastre, Jane Khoury, Matthew Sperling, Brett C Meyer, Kyle B Walsh, Opeolu Adeoye, Joseph P Broderick, W Taylor Kimberly
OBJECTIVE: ST2 is a member of the toll-like receptor superfamily that can alter inflammatory signaling of helper T-cells. We investigated whether soluble ST2 (sST2) could independently predict outcome and hemorrhagic transformation (HT) in the setting of stroke. METHODS: We measured sST2 in patients enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) network biomarker study. 646 patients had plasma samples collected at the time of hospital admission and 210 patients had a second sample collected 48 h after stroke onset...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28811978/development-and-characterization-of-naive-single-type-tumor-antigen-specific-cd8-t-lymphocytes-from-murine-pluripotent-stem-cells
#18
Fengyang Lei, Mohammad Haque, Praneet Sandhu, Swetha Ravi, Jianyong Song, Bing Ni, Songguo Zheng, Deyu Fang, Hongyan Jia, Jin-Ming Yang, Jianxun Song
Optimal approaches to differentiate tumor antigen-specific cytotoxic T lymphocytes (CTLs) from pluripotent stem cells (PSCs) remain elusive. In the current study, we showed that combination of in vitro priming through Notch ligands and in vivo development facilitated the generation of tumor Ag-specific CTLs that effectively inhibited tumor growth. We co-cultured the murine induced PSCs (iPSCs) genetically modified with tyrosinase-related protein 2 (TRP2)-specific T cell receptors with OP9 cell line expressing both Notch ligands Delta-like 1 and 4 (OP9-DL1/DL4) for a week before adoptively transferred into recipient C67BL/6 mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811975/chemotherapeutic-agent-mediated-elimination-of-myeloid-derived-suppressor-cells
#19
REVIEW
Zibing Wang, Brian Till, Quanli Gao
Immunotherapy has shown great promise in the fight against cancer, as evidenced by the clinical efficacy of chimeric antigen receptor T cells in hematologic malignancies and checkpoint blockade in certain solid tumors. However, a considerable number of patients fail to respond to these therapies. Induction of myeloid-derived suppressor cells (MDSCs) by growing tumors has been shown to be one important factor limiting the efficacy of cancer immunotherapy. Recently, several chemotherapeutic agents used in conventional cancer chemotherapy have been found to reduce MDSC numbers in tumor tissues as well as in the peripheral lymphoid organs, and combining these agents with immunotherapy improved survival of tumor-bearing hosts...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811974/ex-vivo-assessment-of-drug-response-on-breast-cancer-primary-tissue-with-preserved-microenvironments
#20
Manuele G Muraro, Simone Muenst, Valentina Mele, Luca Quagliata, Giandomenica Iezzi, Alexandar Tzankov, Walter P Weber, Giulio C Spagnoli, Savas D Soysal
Interaction between cancerous, non-transformed cells, and non-cellular components within the tumor microenvironment plays a key role in response to treatment. However, short-term culture or xenotransplantation of cancer specimens in immunodeficient animals results in dramatic modifications of the tumor microenvironment, thus preventing reliable assessment of compounds or biologicals of potential therapeutic relevance. We used a perfusion-based bioreactor developed for tissue engineering purposes to successfully maintain the tumor microenvironment of freshly excised breast cancer tissue obtained from 27 breast cancer patients and used this platform to test the therapeutic effect of antiestrogens as well as checkpoint-inhibitors on the cancer cells...
2017: Oncoimmunology
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