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https://www.readbyqxmd.com/read/29679556/a-novel-smac-mimetic-apg-1387-exhibited-dual-antitumor-effect-on-hbv-positive-hepatocellular-carcinoma-with-high-expression-of-ciap2-by-inducing-apoptosis-and-enhancing-innate-anti-tumor-immunity
#1
Wentao Pan, Qiuyun Luo, Xianglei Yan, Luping Yuan, Hanjie Yi, Lin Zhang, Baoxia Li, Yuxin Zhang, Jian Sun, Miao-Zhen Qiu, Da-Jun Yang
Check point inhibitor anti-PD1 antibody produced some efficacy in Hepatocellular Carcinoma (HCC) patients previously treated with sorafenib. Unfortunately, HCC patients with hepatitis B virus (HBV) infection did not respond as well as uninfected patients. Previously, SMAC mimetics-the antagonist for inhibitor of apoptosis proteins (IAPs) can rapidly reduce serum hepatitis B virus DNA in animal model. APG-1387 is a novel SMAC-mimetic, small molecule inhibitor targeting inhibitor of apoptosis proteins (IAPs)...
April 18, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29679487/allergen-specific-immunotherapy-induces-regulatory-t-cells-in-an-atopic-dermatitis-mouse-model
#2
Jung U Shin, Seo Hyeong Kim, Ji Yeon Noh, Ji Hye Kim, Kim Hye Ran, Kyoung Yong Jeong, Kyung Hee Park, Jungsoo Lee, Howard Chu, Jae-Hyun Lee, Tai-Soon Yong, Jung-Won Park, Kwang Hoon Lee
BACKGROUND: Several studies have demonstrated that allergen-specific immunotherapy (SIT) can be an effective treatment for atopic dermatitis (AD). However, there is no relevant mouse model to investigate the mechanism and validate the novel modality of SIT in AD. METHODS: NC/Nga mice with induced AD-like skin lesions received a subcutaneous injection of SIT (an extract of the house dust mite Dermatophagoides farinae [DfE]) or placebo for 5 weeks). Clinical and histological improvements of AD-like skin lesions were examined...
April 21, 2018: Allergy
https://www.readbyqxmd.com/read/29678672/genetic-restriction-of-antigen-presentation-dictates-allergic-sensitization-and-disease-in-humanized-mice
#3
Alina Neunkirchner, Bernhard Kratzer, Cordula Köhler, Ursula Smole, Lukas F Mager, Klaus G Schmetterer, Doris Trapin, Victoria Leb-Reichl, Edward Rosloniec, Ronald Naumann, Lukas Kenner, Beatrice Jahn-Schmid, Barbara Bohle, Rudolf Valenta, Winfried F Pickl
BACKGROUND: Immunoglobulin(Ig)E-associated allergies result from misguided immune responses against innocuous antigens. CD4+ T lymphocytes are critical for initiating and perpetuating that process, yet the crucial factors determining whether an individual becomes sensitized towards a given allergen remain largely unknown. OBJECTIVE: To determine the key factors for sensitization and allergy towards a given allergen. METHODS: We here created a novel human T cell receptor(TCR) and human leucocyte antigen (HLA)-DR1 (TCR-DR1) transgenic mouse model of asthma, based on the human-relevant major mugwort (Artemisia vulgaris) pollen allergen Art v 1 to examine the critical factors for sensitization and allergy upon natural allergen exposure via the airways in the absence of systemic priming and adjuvants...
April 5, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29676458/an-optimized-method-to-measure-human-foxp3-regulatory-t-cells-from-multiple-tissue-types-using-mass-cytometry
#4
Nicholas A J Dawson, Avery J Lam, Laura Cook, Romy E Hoeppli, Raewyn Broady, Anne M Pesenacker, Megan K Leving
Mass cytometry has facilitated the discovery of complex immunological networks and immune cell interactions; however, there are limited reports of using this technology to measure expression of intranuclear antigens such as transcription factors. Herein we describe testing of multiple staining methods to detect FOXP3, the lineage-defining transcription factor for regulatory T cells (Tregs), by mass cytometry. A custom paraformaldehyde/saponin-based fixation and permeabilization method was found to be the optimal method for mass cytometry-based Treg detection, yielding the best balance of FOXP3 detection and preserved cell surface marker expression...
April 20, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29676133/-psoralen-inhibits-raw264-7-differentiation-into-osteoclasts-and-bone-resorption-by-regulating-cd4-t-cell-differentiation
#5
Jin-Ping Li, Bao-Ping Xie, Wen-Juan Zhang, Li-Ying Shi, Wei-Juan Li, Ying Zeng, Guo-Xing Gan, Yu-Hong Li
This paper aimed to investigate whether psoralen inhibits the differentiation and bone resorption by regulating CD4+T cell differentiation in RANKL-induced osteoclastogenesis in RAW264.7 cells, and elucidate its mechanism for osteoporosis. CD4+T cells were isolated from spleen cells of Balb/c mice by immunomagnetic separation method. The cells were divided into blank control group and psoralen group. The cells were cultured in 24-well plates and cultured for 3 days, and then they were collected for co-culture experiments after 4 days...
March 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29673942/allergic-patients-with-and-without-allergen-specific-immunotherapy-mount-protective-immune-responses-to-tick-borne-encephalitis-vaccination-in-absence-of-enhanced-side-effects-or-propagation-of-their-th2-bias
#6
Erika Garner-Spitzer, Claudia Seidl-Friedrich, Ines Zwazl, Michael Hofer, Tamar Kinaciyan, Reinhart Jarisch, Karin Stiasny, Gerhard J Zlabinger, Michael Kundi, Ursula Wiedermann
BACKGROUND: Allergic diseases are caused by Th2-driven immune responses and their treatment with specific immunotherapy (SIT) leads to immunomodulation via IL10, TGF-ß and Th1/Tr1 shift. This phase IV, open-label clinical trial investigated whether allergies and SIT treatment influenced immune responses to routine vaccination. METHODS: We studied three groups: 49 allergic patients (allergic group), 21 allergic patients receiving maintenance doses of SIT (SIT group), and 49 non-allergic controls...
April 16, 2018: Vaccine
https://www.readbyqxmd.com/read/29673911/targeting-the-rhoa-rock-pathway-to-regulate-t-cell-homeostasis-in-hypoxia-induced-pulmonary-arterial-hypertension
#7
Cheng Li, Ping-Ping Liu, Dou-Dou Tang, Rong Song, Yi-Qing Zhang, Si Lei, Shang-Jie Wu
BACKGROUND: Hypoxic pulmonary arterial hypertension (PAH) is a crippling disease with limited therapeutic methods. The imbalance of T helper 17 cell (Th17)/regulatory T cell (Treg) plays an important role in the development of Hypoxic PAH. However, whether targeting the ras homolog family member A-Rho kinase (RhoA-ROCK) pathway (activation and inhibition) by lysophosphatidic acid (LPA) and fasudil (FSD) regulate T-cell homeostasis in Hypoxic PAH remain unknown. OBJECTIVE: To examine the effects of LPA and FSD on hypoxic pulmonary vascular remodeling and homeostasis of Th17/Treg cells in Hypoxic PAH...
April 16, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29672594/type-i-interferon-signaling-attenuates-regulatory-t-cell-function-in-viral-infection-and-in-the-tumor-microenvironment
#8
Arunakumar Gangaplara, Craig Martens, Eric Dahlstrom, Amina Metidji, Ameya S Gokhale, Deborah D Glass, Maria Lopez-Ocasio, Rachel Baur, Kishore Kanakabandi, Stephen F Porcella, Ethan M Shevach
Regulatory T cells (Tregs) play a cardinal role in the immune system by suppressing detrimental autoimmune responses, but their role in acute, chronic infectious diseases and tumor microenvironment remains unclear. We recently demonstrated that IFN-α/β receptor (IFNAR) signaling promotes Treg function in autoimmunity. Here we dissected the functional role of IFNAR-signaling in Tregs using Treg-specific IFNAR deficient (IFNARfl/flxFoxp3YFP-Cre) mice in acute LCMV Armstrong, chronic Clone-13 viral infection, and in tumor models...
April 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29672155/an-endogenous-aryl-hydrocarbon-receptor-ahr-ligand-ite-induces-regulatory-t-cells-tregs-and-ameliorates-experimental-colitis
#9
Jessicca D Abron, Narendra P Singh, Manoj K Mishra, Robert L Price, Mitzi Nagarkatti, Prakash S Nagarkatti, Udai P Singh
Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that affects millions of people with high morbidity and health-care cost. The precise etiology of IBD is unknown, but clear evidence suggests that intestinal inflammation is caused by an excessive immune response to mucosal antigens. Recent studies have shown that activation of the aryl hydrocarbon receptor (AhR) induces regulatory T cells (Tregs) and suppresses autoimmune diseases. In the current study, we investigated if nontoxic ligand of AhR, 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), can attenuate dextran sodium sulphate (DSS)-induced colitis...
April 19, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29671652/effects-of-educated-monocytes-with-xenogeneic-mesenchymal-stem-cell-derived-conditioned-medium-in-a-mouse-model-of-chronic-asthma
#10
Hadi Esmaili Gourvarchin Galeh, Seyyed Meysam Abtahi Froushani, Nahideh Afzale Ahangaran, Siamak Naji Hadai
BACKGROUND: This study was conducted to determine the potential of the monocytes educated with rat bone marrow mesenchymal stem cell-derived conditioned medium (MCM) in ameliorating animal model of asthma. METHODS: Chronic asthma was induced in the BALB/c mice using ovalbumin (OVA) sensitization. The monocytes were isolated from blood of mice and supplemented with 50% MCM or negative control media. After 24 h, the cells were designated as "non-educated or educated"...
April 19, 2018: Immunological Investigations
https://www.readbyqxmd.com/read/29671649/lag-3-represents-a-marker-of-cd4-t-cells-with-regulatory-activity-in-patients-with-bone-fracture
#11
Jun Wang, Yunfan Ti, Yicun Wang, Guodong Guo, Hui Jiang, Menghan Chang, Hongbo Qian, Jianning Zhao, Guojing Sun
The lymphocyte activation gene 3 (LAG-3) is a CD4 homolog with binding affinity to MHC class II molecules. It is thought that LAG-3 exerts a bimodal function, such that co-ligation of LAG-3 and CD3 could deliver an inhibitory signal in conventional T cells, whereas, on regulatory T cells, LAG-3 expression could promote their inhibitory function. In this study, we investigated the role of LAG-3 expression on CD4+ T cells in patients with long bone fracture. We found that LAG-3+ cells represented approximately 13% of peripheral blood CD4+ T cells on average...
April 19, 2018: Immunological Investigations
https://www.readbyqxmd.com/read/29671006/regulatory-t-cells-control-endothelial-chemokine-production-and-migration-of-t-cells-into-intestinal-tumors-of-apc-min-mice
#12
Paulina Akeus, Louis Szeponik, Filip Ahlmanner, Patrik Sundström, Samuel Alsén, Bengt Gustavsson, Tim Sparwasser, Sukanya Raghavan, Marianne Quiding-Järbrink
Tumor-infiltrating lymphocytes are crucial for anti-tumor immunity. We have previously shown that regulatory T cells (Treg) are able to reduce T-cell transendothelial migration in vitro and accumulation of effector T cells in intestinal tumors in vivo. Treg depletion also resulted in increased levels of the chemokines CXCL9 and CXCL10 specifically in the tumors. In this study, we investigated the mechanisms for Treg mediated suppression of T-cell migration into intestinal tumors in the APCmin/+ mouse model...
April 18, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29670627/sex-differences-in-adipose-tissue-cd8-t-cells-and-regulatory-t-cells-in-middle-aged-mice
#13
Hilda Ahnstedt, Meaghan Roy-O'Reilly, Monica S Spychala, Alexis S Mobley, Javiera Bravo-Alegria, Anjali Chauhan, Jaroslaw Aronowski, Sean P Marrelli, Louise D McCullough
The prevalence of cardiovascular disease has increased among middle-aged women in the United States, yet has declined in middle-aged men. In experimental stroke, middle-aged females have larger strokes and greater inflammation than age-matched males or younger females. The mechanism underlying this shift from an "ischemia-protected" to an "ischemia-sensitive" phenotype in aging females is unknown. One potential factor is an age-related increase in systemic factors that induce inflammation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29670626/prophylactic-and-therapeutic-effects-of-interleukin-2-il-2-anti-il-2-complexes-in-systemic-lupus-erythematosus-like-chronic-graft-versus-host-disease
#14
Stefan Heiler, Jonas Lötscher, Matthias Kreuzaler, Johanna Rolink, Antonius Rolink
Murine chronic graft-versus-host-disease (cGvHD) induced by injection of parental lymphocytes into F1 hybrids results in a disease similar to systemic lupus erythematosus. Here, we have used DBA/2 T cell injection into (C57BL/6 × DBA/2)F1 (BDF1) mice as a model system to test the prophylactic and therapeutic effects of interleukin-2 (IL-2)/anti-IL-2 immune complexes on the course of cGvHD. Our findings demonstrate that pretreatment with Treg inducing JES6/IL-2 complexes render BDF1 mice largely resistant to induction of cGvHD, whereas pretreatment with CD8+ T cell/NK cell inducing S4B6/IL-2 complexes results in a more severe cGvHD...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29670241/%C3%AE-%C3%AE-t-cells-producing-interleukin-17a-regulate-adipose-regulatory-t-cell-homeostasis-and-thermogenesis
#15
Ayano C Kohlgruber, Shani T Gal-Oz, Nelson M LaMarche, Moto Shimazaki, Danielle Duquette, Hung N Nguyen, Amir I Mina, Tyler Paras, Ali Tavakkoli, Ulrich von Andrian, Alexander S Banks, Tal Shay, Michael B Brenner, Lydia Lynch
γδ T cells are situated at barrier sites and guard the body from infection and damage. However, little is known about their roles outside of host defense in nonbarrier tissues. Here, we characterize a highly enriched tissue-resident population of γδ T cells in adipose tissue that regulate age-dependent regulatory T cell (Treg ) expansion and control core body temperature in response to environmental fluctuations. Mechanistically, innate PLZF+ γδ T cells produced tumor necrosis factor and interleukin (IL) 17 A and determined PDGFRα+ and Pdpn+ stromal-cell production of IL-33 in adipose tissue...
May 2018: Nature Immunology
https://www.readbyqxmd.com/read/29669721/ppar-%C3%AE-contributes-to-immunity-by-cancer-vaccines-that-secrete-gm-csf
#16
Girija Goyal, Karrie Wong, Christopher J Nirschl, Nicholas Souders, Donna Neuberg, Niroshana Anandasabapathy, Glenn Dranoff
Peroxisome proliferator activated receptor-γ (PPARγ) is a lipid-activated nuclear receptor that promotes immune tolerance through effects on macrophages, dendritic cells (DCs), and regulatory T cells (Tregs). Granulocyte-macrophage colony stimulating factor (GM-CSF) induces PPARγ expression in multiple myeloid cell types. GM-CSF contributes to both immune tolerance and protection, but the role of PPARγ in these pathways is poorly understood. Here we reveal an unexpected stimulatory role for PPARγ in the generation of antitumor immunity with irradiated, GM-CSF-secreting tumor-cell vaccines (GVAX)...
April 18, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29669285/kap1-regulates-regulatory-t-cell-function-and-proliferation-in-both-foxp3-dependent-and-independent-manners
#17
Shigeru Tanaka, Christian Pfleger, Jen-Feng Lai, Florence Roan, Shao-Cong Sun, Steven F Ziegler
Regulatory T cells (Tregs) are indispensable for the establishment of tolerance of self-antigens in animals. The transcriptional regulator Foxp3 is critical for Treg development and function, controlling the expression of genes important for Tregs through interactions with binding partners. We previously reported KAP1 as a binding partner of FOXP3 in human Tregs, but the mechanisms by which KAP1 affects Treg function were unclear. In this study, we analyzed mice with Treg-specific deletion of KAP1 and found that they develop spontaneous autoimmune disease...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29666503/regulatory-t-cell-derived-extracellular-vesicles-modify-dendritic-cell-function
#18
Sim L Tung, Dominic A Boardman, Monica Sen, Marilena Letizia, Qi Peng, Nicole Cianci, Laura Dioni, Leo M Carlin, Robert Lechler, Valentina Bollati, Giovanna Lombardi, Lesley A Smyth
Regulatory T cells (Treg) are a subpopulation of T cells that maintain tolerance to self and limit other immune responses. They achieve this through different mechanisms including the release of extracellular vesicles (EVs) such as exosomes as shown by us, and others. One of the ways that Treg derived EVs inhibit target cells such as effector T cells is via the transfer of miRNA. Another key target for the immunoregulatory function of Tregs is the dendritic cells (DCs). In this study we demonstrate directly, and for the first time, that miRNAs are transferred from Tregs to DCs via Treg derived EVs...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666297/phase-ii-study-of-everolimus-in-metastatic-malignant-melanoma-ncctg-n0377-alliance
#19
Jesus Vera Aguilera, Ravi D Rao, Jacob B Allred, Vera J Suman, Harold E Windschitl, Judith S Kaur, William J Maples, Val J Lowe, Edward T Creagan, Lori A Erickson, Svetomir Markovic
LESSONS LEARNED: Everolimus does not have sufficient activity to justify its use as single agent in metastatic melanoma.Patients treated with 10 mg per day dose were most likely to require dose reductions.Everolimus appeared to reduce the numbers of regulatory T cells in approximately half of the treated patients; unfortunately, these effects were not correlated with clinical outcomes. BACKGROUND: Everolimus (RAD-001) is an orally active rapamycin analogue shown in preclinical data to produce cytostatic cell inhibition, which may be potentially beneficial in treating melanoma...
April 17, 2018: Oncologist
https://www.readbyqxmd.com/read/29665919/-effect-and-clinical-significance-of-bortezomib-and-thalidomide-on-the-memory-t-cells-subsets-and-regulatory-t-cells-in-peripheral-blood-of-patients-with-multiple-myeloma
#20
Ling-Ling Shi, Han-Qing Li, Jian-Gang Mei, Xiao-Gang Zhou, Feng Li, Ping Song, Yong-Ping Zhai
OBJECTIVE: To investigate the effects of bortezomib(BTZ) and thalidomide(TM) on peripheral blood memory T-cells (Tm ) and regulatory T cells(Tregs) in patients with multiple myeloma(MM). METHODS: Eighty-six MM patients received 2 courses of chemotherapy were divided into effective (partial response at least) group (63 cases) and ineffective (no partial response) group (17 cases) according to therapeutic efficacy; these 80 patients were divided into BTZ group (38 cases) and TM group (42 cases) yet according to therapeutic regimens, 20 newly diagnosed MM patients were used as baseline group, 30 healthy volunteers were used as healthy control group...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
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