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https://www.readbyqxmd.com/read/28931869/dermatophagoides-pteronyssinus-immunotherapy-changes-the-t-regulatory-cell-activity
#1
M Gonzalez, I Doña, F Palomares, P Campo, M J Rodriguez, C Rondon, F Gomez, T D Fernandez, J R Perkins, M M Escribese, M J Torres, C Mayorga
Subcutaneous specific immunotherapy (SCIT) has been shown to modify the Dermatophagoides pteronissinus (DP) allergic response, characterized by generation of Treg cells. However, studies have reported no changes in the proportion of Treg cells after immunotherapy, indicating that the effects may be due to modifications in their regulatory activities. We aimed to determine whether Tregs generated by DP-SCIT can switch the allergic response to tolerant and study the involvement of suppressive cytokines on it...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931834/mild-hypothermia-provides-treg-stability
#2
Marek- Trzonkowska Natalia, Piekarska Karolina, Filipowicz Natalia, Piotrowski Arkadiusz, Gucwa Magdalena, Vogt Katrin, Sawitzki Birgit, Siebert Janusz, Trzonkowski Piotr
Regulatory T cells (Tregs) play crucial role in maintenance of peripheral tolerance. Recent clinical trials confirmed safety and efficacy of Treg treatment of deleterious immune responses. However, Tregs lose their characteristic phenotype and suppressive potential during expansion ex vivo. Therefore, multiple research teams have been studding Treg biology in aim to improve their stability in vitro. In the current paper, we demonstrate that mild hypothermia of 33 °C induces robust proliferation of Tregs, preserves expression of FoxP3, CD25 and Helios, and prevents TSDR methylation during culture in vitro...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#3
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28930796/navigating-t-cell-immunometabolism-in-transplantation
#4
Naoki Tanimine, Laurence A Turka, Bhavana Priyadharshini
Recently, a new discipline termed "immunometabolism" has transformed the field of immunology. It encompasses the study of the intrinsic metabolic pathways of different immune subsets and their impact on cellular fate and function. For instance, broadly speaking, pro-inflammatory cells depend upon glycolysis and glutamine oxidation while cells involved in anti-inflammatory response such as Foxp3+ regulatory T cells (Tregs) utilize predominantly fatty acid oxidation. However, while a useful paradigm, this actually is a reductionist view and the engagement of these metabolic pathways is not mutually exclusive between these subsets...
September 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28930662/the-kinase-mtorc1-promotes-the-generation-and-suppressive-function-of-follicular-regulatory-t-cells
#5
Lifan Xu, Qizhao Huang, Haoqiang Wang, Yaxing Hao, Qiang Bai, Jianjun Hu, Yiding Li, Pengcheng Wang, Xiangyu Chen, Ran He, Bingshou Li, Xia Yang, Tingting Zhao, Yanyan Zhang, Yifei Wang, Juanjuan Ou, Houjie Liang, Yuzhang Wu, Xinyuan Zhou, Lilin Ye
Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930651/driving-rel-iant-tregs-toward-an-identity-crisis
#6
Amy Li, Tyler Jacks
Inhibiting Treg cell function in tumors is an attractive strategy to improve anti-cancer immunity. In a pair of papers in Immunity and Cell, Ghosh and colleagues show that the canonical NF-κB subunits p65 and c-Rel have non-redundant, critical roles in promoting Treg cell development and function (Oh et al., 2017). Targeting c-Rel blunts Treg cell immunosuppressive activity in the tumor microenvironment and enhances anti-tumor T cell responses (Grinberg-Bleyer et al., 2017).
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930556/osteoimmunology-the-nexus-between-bone-and-immune-system
#7
Hamid Y Dar, Zaffar Azam, Rajaneesh Anupam, Rajesh K Mondal, Rupesh K Srivastava
Osteoimmunology is an interdisciplinary research field which combines the existing fields of osteology (bone biology) and immunology under one umbrella. The observation that contributed enormously to the emergence of osteoimmunology as an independent field of investigation was the enhanced bone loss in various inflammatory bone diseases such as rheumatoid arthritis, osteoporosis and periodontitis. T helper cells (Th1, Th2, Treg and Th17) along with various other immune cells (B cells, DC, macrophages etc.) are actively involved in bone homeostasis...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28929455/role-of-mast-cells-in-regulation-of-t-cell-responses-in-experimental-and-clinical-settings
#8
REVIEW
Daniel Elieh Ali Komi, Korneel Grauwet
Mast cells secrete a wide spectrum of stored or newly synthesized pro-inflammatory, anti-inflammatory, and/or immunosuppressive mediators and express several costimulatory and inhibitory surface molecules. Mast cells finely tune activities of T cells, B cells, and regulatory cells and effectively contribute to the development of different T cell-associated responses by influencing their recruitment, activation, proliferation, and differentiation. The interaction between mast cells and T cells, with regard to cellular functionality and immune responses, can be assessed in both activating and inhibitory regulations...
September 19, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28929191/overview-of-lag-3-expressing-il-10-producing-regulatory-t-cells
#9
Keishi Fujio, Kazuhiko Yamamoto, Tomohisa Okamura
Regulatory T cells (Treg cells) play crucial roles in the induction of peripheral tolerance to self- and foreign-antigens. IL-10-producing regulatory T cells (IL-10-producing Treg cells) constitute a Treg cell subset characterized by the production of high amounts of IL-10, cytokine-mediated immunosuppressive capabilities, and independence of Foxp3 expression for their suppressive activity. In the past decade, identifying naturally occurring IL-10-producing Treg cells was difficult due to the lack of suitable surface markers...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28926770/1-25-oh-2d3-induces-regulatory-t-cell-differentiation-by-influencing-the-vdr-plc-%C3%AE-1-tgf-%C3%AE-1-pathway
#10
Qiang Zhou, Shengying Qin, Jinyan Zhang, Lin Zhon, Zhihai Pen, Tonghai Xing
Vitamin D has been recommended as an immune modulator in recent years, in addition to regulating calcium-phosphorous-bone metabolism. Clinical studies on organ transplantation found that vitamin D sufficiency patients were less likely to develop acute cellular rejection within one year after transplantation compared to those with vitamin D deficiency. Thus, a high percentage of regulatory T cells might play a key role in preventing acute cellular rejection (ACR). In this report, we studied the specific effects of 1,25(OH)2D3 on human T cell diff ;erentiation, and determined the potential molecule mechanism behind...
September 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28926619/liver-x-receptor-activation-promotes-differentiation-of-regulatory-t-cells
#11
Martin Herold, Johanna Breuer, Stephanie Hucke, Percy Knolle, Nicholas Schwab, Heinz Wiendl, Luisa Klotz
The nuclear receptor Liver X Receptor (LXR) is a ligand-activated transcription factor that has been implicated in control of chronic inflammation by downregulating pro-inflammatory T cell responses. An impaired function of regulatory T cells, a subset of CD4+ T cells with a crucial role in maintaining lymphocytes homeostasis and immune regulation, is frequently observed in chronic inflammatory diseases. We observed that pharmacological activation of LXR in T cells not only resulted in a thorough suppression of Th1 and Th17 polarization in vitro, but also significantly induced regulatory T cells (Treg) cell differentiation in a receptor-specific fashion...
2017: PloS One
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#12
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28923634/variation-of-cd4-cd25-foxp3-regulatory-t-cells-and-th17-cells-in-the-peripheral-blood-of-human-liver-allograft-patients-with-long-term-survival
#13
G Shi, Q Zeng, Z Zhao, W Li, J Dou
BACKGROUND: Monitoring of peripheral blood (PB) lymphocyte subpopulation counts may be useful to underlie immune status after liver transplantation (LT). We aimed at exploring the variation of regulatory cells and Th17 in the PB of liver allograft patients with long-term survival. METHODS: Forty-two patients who took FK506 drugs were divided into 3 groups: patients who survived for 6 months to 3 years were in the Tac1 group (n = 15), those who survived for 3-10 years were in the Tac2 group (n = 15), and those who survived for >10 years were in the Tac3 group (n = 12)...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923424/depletion-of-regulatory-t-cells-by-anti-icos-antibody-enhances-anti-tumor-immunity-of-tumor-cell-vaccine-in-prostate-cancer
#14
Lijun Mo, Qianmei Chen, Xinji Zhang, Xiaojun Shi, Lili Wei, Dianpeng Zheng, Hongwei Li, Jimin Gao, Jinlong Li, Zhiming Hu
ICOS(+)Treg cells exert important immunosuppressive effects in tumor immunity. We adopt a combination approach of ICOS(+)Treg cells depletion with tumor cell vaccine to evaluate anti-tumor immunity in mouse prostate cancer model. Streptavidin (SA)-mGM-CSF surface-modified RM-1 cells were prepared as the vaccine and the mouse subcutaneous prostate tumor model was used to evaluate the immunity. Tumor growth, flow cytometry, immunohistochemistry, immunofluorescence and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the therapeutic effects...
September 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28923131/innate-and-adaptive-immune-response-to-chronic-pulmonary-infection-of-hyphae-of-aspergillus-fumigatus-in-a-new-murine-model
#15
Fengyuan Wang, Caiyun Zhang, Yuan Jiang, Caixia Kou, Qingtao Kong, Nanbiao Long, Ling Lu, Hong Sang
PURPOSE: The pathogenesis of chronic pulmonary aspergillosis (CPA) has seldom been studied due partly to a lack of animal models. Since hypha is the main morphology colonizing the airway in CPA, it's critical to study the immune reaction to chronic pulmonary infection of hyphae of Aspergillus fumigatus, which also has seldom been studied in vivo before. METHODOLOGY: We established a novel murine model of chronic pulmonary infection of hyphae by challenging immunocompetent mice with tightly-structured hyphae balls intratracheally, and described the ensuing immunoreaction to hyphae and conidia, and the pathogenesis of CPA...
September 19, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28922374/fractional-laser-exposure-induces-neutrophil-infiltration-n1-phenotype-into-the-tumor-and-stimulates-systemic-anti-tumor-immune-response
#16
Masayoshi Kawakubo, Shadmehr Demehri, Dieter Manstein
BACKGROUND: Ablative fractional photothermolysis (aFP) using a CO2 laser generates multiple small diameter tissue lesions within the irradiation field. aFP is commonly used for a wide variety of dermatological indications, including treatment of photodamaged skin and dyschromia, drug delivery and modification of scars due to acne, surgical procedures and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression and inducing anti-tumor immunity, which is in marked contrast to current indications of aFP...
2017: PloS One
https://www.readbyqxmd.com/read/28921730/comparison-of-the-percentages-of-cd4-%C3%A2-cd25-high-%C3%A2-foxp3-cd4-%C3%A2-cd25-low-%C3%A2-foxp3-and-cd4-%C3%A2-foxp3-tregs-in-the-umbilical-cord-blood-of-babies-born-to-mothers-with-and-without-preeclampsia
#17
Farha El-Chennawi, Ibrahim Mohamed Rageh, Amira Ibrahim Mansour, Mohammed Ibrahim Darwish, Ashraf Antar Elghzaly, Basma El Sayed Sakr, Khaled Mohsen Elbaz
PROBLEM: Little is known about how preeclampsia affects regulatory T-cell count and functions in umbilical cord blood of babies born to preeclamptic mothers. Here, we analyze the percentage of CD4(+)  CD25(high)  FOXP3(+) , CD4(+)  CD25(low)  FOXP3(+) , and CD4(+)  FOXP3(+) Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia. METHOD OF STUDY: The percentage of umbilical cord blood CD4(+)  CD25(high)  FOXP3(+) , CD4(+)  CD25(low)  FOXP3(+) , and CD4(+)  FOXP3(+) Tregs were analyzed by flow cytometry...
September 16, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#18
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920001/zoledronic-acid-inhibits-nfat-and-il-2-signaling-pathways-in-regulatory-t-cells-and-diminishes-their-suppressive-function-in-patients-with-metastatic-cancer
#19
Dhifaf Sarhan, Caroline Leijonhufvud, Shannon Murray, Kristina Witt, Christina Seitz, Majken Wallerius, Hanjing Xie, Anders Ullén, Ulrika Harmenberg, Elisabet Lidbrink, Charlotte Rolny, John Andersson, Andreas Lundqvist
Regulatory T cells (Treg) suppress anti-tumor immune responses and their infiltration in the tumor microenvironment is associated with inferior prognosis in cancer patients. Thus, in order to enhance anti-tumor immune responses, selective depletion of Treg is highly desired. We found that treatment with zoledronic acid (ZA) resulted in a selective decrease in the frequency of Treg that was associated with a significant increase in proliferation of T cells and natural killer (NK) cells in peripheral blood of patients with metastatic cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919985/human-tumor-derived-exosomes-tex-regulate-treg-functions-via-cell-surface-signaling-rather-than-uptake-mechanisms
#20
Laurent Muller, Patricia Simms, Chang-Sook Hong, Michael I Nishimura, Edwin K Jackson, Simon C Watkins, Theresa L Whiteside
Tumor-derived exosomes (TEX) are ubiquitously present in the tumor microenvironment and plasma of cancer patients. TEX carry a cargo of multiple stimulatory and inhibitory molecules and deliver them to recipient cells, serving as a communication network for the tumor. The mechanisms TEX use for delivering messages to recipient cells were evaluated using PKH26-labeled TEX produced by cultured human tumor cells, exosomes produced by dendritic cells-derived exosomes (DEX), or exosomes isolated from plasma of cancer patients (EXO)...
2017: Oncoimmunology
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