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https://www.readbyqxmd.com/read/28732437/effect-of-microrna-21-transfection-on-in-vitro-differentiation-of-human-naive-cd4-t-cells-to-regulatory-t-cells
#1
Haideh Namdari, Mojgan Ghayedi, Jamshid Hadjati, Farhad Rezaei, Kurosh Kalantar, Parisa Rahimzadeh, Eisa Salehi
Regulatory T cells (Tregs) are important components of the immune system that modulate responses of other cells. These cells are involved in peripheral tolerance mechanisms, so defect in development and function of these cells can result in autoimmune disease. Increasing evidence supports the role of microRNAs-21 (miR-21) in the regulation of forkhead box P3 (Foxp3) expression in Tregs. We aimed to determine whether miR-21 transfection to naive CD4+ T cells can be useful in generation of iTregs in-vitro. We investigated in-vitro differentiation of miR-21-transfected naive CD4+ T cells to iTregs and compared these iTregs to cytokine-differentiated iTregs and control group...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28731226/curcumin-converts-foxp3-regulatory-t-cells-to-t-helper-1-cells-in-patients-with-lung-cancer
#2
JianYong Zou, ChunHua Su, HongHe Luo, YiYan Lei, Bo Zeng, HaoShuai Zhu, ZhenGuang Chen
The regulatory T cells (Treg) play an important role in the tumor tolerance. The methods to regulate the Treg population in cancer-bearing hosts are limited currently. The effect of curcumin on inhibiting cancer has been recognized, but the mechanism remains elusive. This study tests a hypothesis that administration of curcumin down regulates Tregs in lung cancer (LC) patients. In this study, a group of LC patients was treated with curcumin. The peripheral Tregs and T helper (Th) 1 cells were analyzed by flow cytometry...
July 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28731046/pd-l1-expression-and-the-immune-microenvironment-in-primary-invasive-lobular-carcinomas-of-the-breast
#3
Elizabeth D Thompson, Janis M Taube, Rebecca J Asch-Kendrick, Aleksandra Ogurtsova, Haiying Xu, Rajni Sharma, Alan Meeker, Pedram Argani, Leisha A Emens, Ashley Cimino-Mathews
Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (<5%); 2+ (5-10%); 3+ (10-15%); or 4+ (>50%)...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28729731/anti-asthmatic-effect-of-pitavastatin-through-aerosol-inhalation-is-associated-with-cd4-cd25-foxp3-t-cells-in-an-asthma-mouse-model
#4
Songquan Wu, Ruhui Yang, Guangli Wang
Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-A) reductase, and studies have shown that statins also have anti-inflammatory and immunomodulatory properties. The purpose of this study was to investigate the anti-asthmatic effects of pitavastatin, a type of statin, in an asthma mouse model. Mice were sensitized and challenged with ovalbumin (OVA) to establish the asthma model. These mice were then treated with inhaled pitavastatin (5 mg/kg) or dexamethasone (2 mg/kg), the latter of which served as a positive control...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729608/programmed-death-one-homolog-maintains-the-pool-size-of-regulatory-t-cells-by-promoting-their-differentiation-and-stability
#5
Qi Wang, Jianwei He, Dallas B Flies, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is an immunoglobulin superfamily molecule and primarily acts as a coinhibitor in the initiation of T cell response to antigens. Here, we report that genetic ablation of PD-1H in mice blocks the differentiation of naive T cells to Foxp3(+) inducible Treg cells (iTreg) with a significant decrease of iTreg in lymphoid organs. This effect of PD-1H is highly specific for iTreg because both naturally generated iTreg in gut-related tissues and in vitro induced iTreg by TGF-β were decreased whereas the genesis of natural Treg (nTreg) remains normal...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729148/clinical-grade-expanded-tregs-prevent-gvhd-while-allowing-a-powerful-t-cell-dependent-gvl-effect-in-murine-models
#6
B Del Papa, L Ruggeri, E Urbani, S Baldoni, D Cecchini, T Zei, R Iacucci Ostini, B Crescenzi, A Carotti, A Pierini, P Sportoletti, P Di Bartolomeo, F Falzetti, C Mecucci, A Velardi, M F Martelli, M Di Ianni
We developed a GMP-compatible expansion protocol, to improve number and purity of Tregs available for clinical trials. Six clinical grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation and rapamycin for 19 days achieving a median of 8.5 fold (6.25-13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced. The in vitro suppression assay showed a strong MLR inhibition...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28728868/pdl1-expression-in-desmoplastic-melanoma-is-associated-with-tumor-aggressiveness-and-progression
#7
Stefan Kraft, Maria-Teresa Fernandez-Figueras, Nina A Richarz, Keith T Flaherty, Mai P Hoang
BACKGROUND: The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear. METHODS: We correlated PDL1, p53, and Ki-67 expression with CD8(+) and FoxP3(+) immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas. RESULTS: Tumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis...
July 17, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28728239/-effect-of-hydrogen-rich-saline-on-the-cd4-cd25-foxp3-treg-cells-of-allergic-rhinitis-guinea-pigs-model
#8
F F Xu, S Q Yu, C L Zhao, N Che, L Jin, Q L Wang, R M Ge
Objective: To explore the effect of hydrogen-rich saline on the CD4(+) CD25(+) Foxp3(+) Treg cells in a guinea pig model of allergic rhinitis (AR) and investigate the underling anti-inflammatory mechanism. Methods: Using random number table, eighteen guinea pigs were divided into three groups (control group/AR group/HRS group, n=6 of each group). AR guinea pig model was built with ovalbumin and aluminum. The guinea pigs were injected with hydrogen-rich saline (HRS group) for ten days after sensitation. And control group was injected with equal normal saline at the same time...
July 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28727997/therapeutic-intranasal-instillation-of-allergen-loaded-microbubbles-suppresses-experimental-allergic-asthma-in-mice
#9
Blaise Corthésy, Gilles Bioley
Despite proven efficiency, subcutaneous immunotherapy for aeroallergens is impaired by the duration of the protocol, the repeated injections and potential side-effects associated with the doses of allergen administered. Intranasal delivery of immunotherapeutic agents may overcome several of these drawbacks, provided that an efficient allergen delivery vehicle can be identified. This study evaluates whether intranasally delivered gas-filled microbubble (MB)-associated ovalbumin (OVA), used as a model allergen, can serve as a therapeutic treatment in a mouse model of established allergic asthma...
July 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28724939/fatty-acid-uptake-in-t-cell-subsets-using-a-quantum-dot-fatty-acid-conjugate
#10
Megan E Muroski, Jason Miska, Alan L Chang, Peng Zhang, Aida Rashidi, Haley Moore, Aurora Lopez-Rosas, Yu Han, Maciej S Lesniak
Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by T cell subsets is important for understanding tumor immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with superior sensitivity and flexibility to any of the previously commercially available alternatives. For the first time, we demonstrate that this nanoparticle can be used as a specific measure of fatty acid uptake by T cells both in-vitro and in-vivo...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724788/multiparametric-immune-profiling-in-hpv-oral-squamous-cell-cancer
#11
Zipei Feng, Daniel Bethmann, Matthias Kappler, Carmen Ballesteros-Merino, Alexander Eckert, R Bryan Bell, Allen Cheng, Tuan Bui, Rom Leidner, Walter J Urba, Kent Johnson, Clifford Hoyt, Carlo B Bifulco, Juergen Bukur, Claudia Wickenhauser, Barbara Seliger, Bernard A Fox
Evaluation of T lymphocyte frequency provides prognostic information for patients with oral squamous cell cancer (OSCC). However, the effect of simultaneously evaluating T cell frequency and assessing suppressive elements and defects in antigen-processing machinery (APM) has not been clarified. Simultaneous characterization of CD3+, CD8+, FoxP3+, CD163+, and PD-L1+ cells using multispectral imaging was performed on sections from 119 patients with HPV- OSCC. Expression of β2-microglobulin, MHC class I heavy chain, and large multifunctional peptidase 10 was quantified, and all data were correlated with patient outcome...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724578/induction-of-regulatory-t-cells-and-its-regulation-with-insulin-like-growth-factor-insulin-like-growth-factor-binding-protein-4-by-human-mesenchymal-stem-cells
#12
Ippei Miyagawa, Shingo Nakayamada, Kazuhisa Nakano, Kaoru Yamagata, Kei Sakata, Kunihiro Yamaoka, Yoshiya Tanaka
Human mesenchymal stem cells (MSCs) are multipotent and exert anti-inflammatory effects, but the underlying mechanism remains to be elucidated. In the current study, we investigated the regulatory mechanism of regulatory T cell (Treg) induction through the growth factors released by human MSCs. Human naive CD4(+) T cells were stimulated with anti-CD3/28 Abs and cocultured with human MSC culture supernatant for 48 h. The proliferation and cytokine production of CD4(+) T cells and surface molecule expression on CD4(+) T cells were evaluated...
July 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28722666/tumor-pd-l1-status-and-cd8-tumor-infiltrating-t-cells-markers-of-improved-prognosis-in-oropharyngeal-cancer
#13
Astrid De Meulenaere, Tijl Vermassen, Sandrine Aspeslagh, Philippe Deron, Fréderic Duprez, Debby Laukens, Jo Van Dorpe, Liesbeth Ferdinande, Sylvie Rottey
INTRODUCTION: The aim of this study was to evaluate the expression of PD-L1 in oropharyngeal squamous cell carcinoma. Its relation with clinicopathological variables such as amount and type of tumor infiltrating lymphocytes, HPV status and survival was also determined. RESULTS: Positive PD-L1 status for the SP142 clone related with improved overall survival in oropharyngeal squamous cell carcinoma. Tumors heavily infiltrated by tumor infiltrating lymphocytes were also linked with better outcome, and this as well for the total number of tumor infiltrating lymphocytes as for the CD3+ and CD8+ T cell count...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#14
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
July 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28720146/analysis-of-long-term-cd4-cd25highcd127-t-reg-cells-kinetics-in-peripheral-blood-of-lung-transplant-recipients
#15
Davide Piloni, Monica Morosini, Sara Magni, Alice Balderacchi, Luigia Scudeller, Emanuela Cova, Tiberio Oggionni, Giulia Stella, Carmine Tinelli, Filippo Antonacci, Andrea Maria D'Armini, Federica Meloni
BACKGROUND: The role of CD4(+)CD25(high)CD127(-) T-reg cells in solid-organ Transplant (Tx) acceptance has been extensively studied. In previous studies on kidney and liver recipients, peripheral T-reg cell counts were associated to graft survival, while in lung Tx, there is limited evidence for similar findings. This study aims to analyze long term peripheral kinetics of T-reg-cells in a cohort of lung recipients and tests its association to several clinical variables. METHODS: From jan 2009 to dec 2014, 137 lung Tx recipients were submitted to an immunological follow up (median: 105...
July 18, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28719617/microrna-155-deficiency-leads-to-decreased-autoantibody-levels-and-reduced-severity-of-nephritis-and-pneumonitis-in-pristane-induced-lupus
#16
Harald Leiss, Wilhelm Salzberger, Barbara Jacobs, Irina Gessl, Nicolas Kozakowski, Stephan Blüml, Antonia Puchner, Attila Kiss, Bruno K Podesser, Josef S Smolen, Georg H Stummvoll
OBJECTIVE: We herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus. MATERIALS AND METHODS: Systemic lupus in miR155-deficient and wild type mice was induced upon injection of pristane and analyzed after 8 months, PBS-injected mice served as controls. Glomerulonephritis and pneumonitis were quantified using the kidney biopsy score and a newly adapted histomorphometric image analysis system; lung tissue was further analyzed by tissue cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28716029/foxp3-promotes-tumor-growth-and-metastasis-by-activating-wnt-%C3%AE-catenin-signaling-pathway-and-emt-in-non-small-cell-lung-cancer
#17
Shucai Yang, Yi Liu, Ming-Yue Li, Calvin S H Ng, Sheng-Li Yang, Shanshan Wang, Chang Zou, Yujuan Dong, Jing Du, Xiang Long, Li-Zhong Liu, Innes Y P Wan, Tony Mok, Malcolm J Underwood, George G Chen
BACKGROUND: The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). METHODS: One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed...
July 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28713387/human-cd6-down-modulation-following-t-cell-activation-compromises-lymphocyte-survival-and-proliferative-responses
#18
Esther Carrasco, Cristina Escoda-Ferran, Núria Climent, Cristina Miró-Julià, Inês T Simões, Mario Martínez-Florensa, Adelaida Sarukhan, Esther Carreras, Francisco Lozano
Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen-presenting cells and likely modulating T-cell receptor (TCR) signaling. Here, we show that in vitro activation of human T cells under different TCR-ligation conditions leads to surface downregulation of CD6 expression. This phenomenon was (i) concomitant to increased levels of soluble CD6 (sCD6) in culture supernatants, (ii) partially reverted by protease inhibitors, (iii) not associated to CD6 mRNA down-regulation, and (iv) reversible by stimulus removal...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28713192/foxp3-allelic-variants-and-haplotype-structures-are-associated-with-aggressive-breast-cancer-subtypes
#19
Bruna Karina Banin Hirata, Roberta Losi Guembarovski, Glauco Akelinghton Freire Vitiello, Alda Losi Guembarovski, Karen Brajão de Oliveira, Maria Angelica Ehara Watanabe
FOXP3 genetic polymorphisms have been associated with cancer development and prognosis. In this context, the present study aimed to evaluate the g.10403A>G (rs2232365) polymorphisms and g.8048A>C (rs3761548), in aggressive breast cancer (BC) subtypes, including, Luminal B HER2+ (LB), HER2-enriched (HER2+), and triple-negative (TN). Polymerase chain reaction followed by enzymatic restriction was performed to genotyping 117 BC samples and 300 controls. A significant association of AA genotype (g.10403A>G) in relation to BC susceptibility (OR = 1...
2017: Disease Markers
https://www.readbyqxmd.com/read/28712929/exosomes-from-osteosarcoma-and-normal-osteoblast-differ-in-proteomic-cargo-and-immunomodulatory-effects-on-t-cells
#20
Ryan M Troyer, Carl E Ruby, Cheri P Goodall, Liping Yang, Claudia S Maier, Hassan A Albarqi, Jacqueline V Brady, Kallan Bathke, Oleh Taratula, Dan Mourich, Shay Bracha
BACKGROUND: Canine osteosarcoma (OSA) is the most common cancer of the appendicular skeleton and is associated with high metastatic rate to the lungs and poor prognosis. Recent studies have shown the impact of malignant-derived exosomes on immune cells and the facilitation of immune evasion. In the current study, we have characterized the proteomic profile of exosomes derived from healthy osteoblasts and osteosarcoma cell lines. We investigated the direct impact of these exosomes on healthy T cells...
July 13, 2017: Experimental Cell Research
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