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https://www.readbyqxmd.com/read/29224017/the-il-2-anti-il-2-complex-attenuates-cardiac-ischaemia-reperfusion-injury-through-expansion-of-regulatory-t-cells
#1
Junhui Xiao, Kunwu Yu, Ming Li, Chuanyin Xiong, Yuzhen Wei, Qiutang Zeng
BACKGROUND/AIMS: Regulatory T cells (Tregs) can suppress immunologic damage in myocardial ischaemia/reperfusion injury (MIRI), however, the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate MIRI in mice. METHODS: Myocardial I/R was surgically induced in male C57BL/6 mice, aged 8-10 weeks, that were randomly assigned to 1) sham group (Sham), 2) Phosphate Buffered Saline (PBS), 3) IL-2-anti-IL-2 Ab complex (IL-2C), or 4) sham group, 5) PBS, 6) IL-2C after MIRI, or 7) IL-2C, 8) IL-2C+anti-CD25 mAbs, or 9) IL-2C; 10) IL-2C+anti-TGF-β1 mAbs, 11) IL-2C+anti-IL-10 mAbs...
December 7, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29223407/stat3-mediated-epigenetic-silencing-of-foxp3-in-lada-t-cells-is-regulated-through-hdac5-and-dnmt1
#2
Can Hou, Yanjun Zhong, Zhen Wang, Zhao Ming, Gan Huang, Lin Ouyang, Yijun Li, Qianjin Lu, Zhiguang Zhou
In LADA patients, Tregs are reduced and FOXP3 is downregulated in CD4+ T cells, but the etiology remains unclear. Our study included in 20 LADA patients and 20 healthy control patients. qRT-PCR results showed that STAT3, HDAC3, HDAC5, SIRT1, DNMT1 and DNMT3b mRNAs were significantly upregulated in LADA CD4+ T cells than controls, while FOXP3 mRNA significantly decreased. p-STAT3, STAT3, DNMT1 and DNMT3b expressions were increased demonstrated by western blot. ChIP-PCR suggested that p-STAT3 binds to the Foxp3 promoter, meanwhile, histone H3 acetylation at K9 and K14 of FOXP3 promoter were significantly lower than controls...
December 6, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29223294/glucocorticoid-hormone-treatment-enhances-the-cytokine-production-of-regulatory-t-cells-by-upregulation-of-foxp3-expression
#3
Emese Ugor, Lilla Prenek, Ramóna Pap, Gergely Berta, Dávid Ernszt, József Najbauer, Péter Németh, Ferenc Boldizsár, Tímea Berki
OBJECTIVE: Despite the fact that glucocorticoids (GC) are important therapeutic tools, their effects on regulatory T cells (Treg) are not well defined. The aim of our work was to investigate how GCs influence in vivo the thymic (tTreg) and peripheral Treg (pTreg) differentiation, survival and cytokine production. METHODS: Tregs were detected with flow cytometry in lymphatic organs of 4-6 weeks old BALB/c mice after repeated (2-4days), high-dose in vivo GC treatment using CD4/CD25 cell surface and Foxp3/IL-10/TGFβ/glucocorticoid receptor (GR) intracellular staining...
October 6, 2017: Immunobiology
https://www.readbyqxmd.com/read/29222448/effect-of-qianghuo-erhuang-decoction-on-t-regulatory-and-t-helper-17-cells-in-treatment-of-adjuvant-induced-arthritis-in-rats
#4
Can Qian, Mei Kuang, Yong Wang
QianghuoErhuang Decoction (QED) is an effective recipe in treating rheumatoid arthritis. The present study aimed to explore the effects of QED on Treg and Th17 in adjuvant arthritis (AA) model. The study included 6 group rats: normal control group, AA group, AA + methotrexate (MTX) group, AA + high, moderate, and low dose QED groups. The arthritis score was significantly decreased in the MTX and high-dose QED groups compared with the AA group on days 24 and 28 (P < 0.01), respectively. The synovial tissue inflammation was attenuated by histological observation, and the proliferation of splenocytes was significantly inhibited in MTX and high-dose QED groups (P < 0...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29221287/anti-cancer-activity-of-dose-fractioned-mpe-bevacizumab-regimen-is-paralleled-by-immune-modulation-in-advanced-squamous-nslc-patients
#5
Pierpaolo Pastina, Valerio Nardone, Stefania Croci, Giuseppe Battaglia, Francesca Vanni, Cristiana Bellan, Marcella Barbarino, Veronica Ricci, Susan Costantini, Francesca Capone, Cirino Botta, Mayra Rachele Zarone, Gabriella Misso, Mariarosaria Boccellino, Michele Caraglia, Antonio Giordano, Piero Paladini, Pierfrancesco Tassone, Pierosandro Tagliaferri, Maria Grazia Cusi, Luigi Pirtoli, Pierpaolo Correale
Background: Results from the BEVA2007 trial, suggest that the metronomic chemotherapy regimen with dose-fractioned cisplatin and oral etoposide (mPE) +/- bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), shows anti-angiogenic and immunological effects and is a safe and active treatment for metastatic non-small cell lung cancer (mNSCLC) patients. We carried out a retrospective analysis aimed to evaluate the antitumor effects of this treatment in a subset of patients with squamous histology...
September 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29221197/rank-expression-in-ebv-positive-nasopharyngeal-carcinoma-metastasis-a-ready-to-treat-target
#6
Carlo Resteghini, Salvatore Alfieri, Pasquale Quattrone, Francesca Dominoni, Giovanna Garzone, Ester Orlandi, Laura Locati, Cristiana Bergamini, Donata Galbiati, Nicola Alessandro Iacovelli, Carlo Fallai, Lisa Licitra, Paolo Bossi
Epstein Barr Virus (EBV) related Nasopharyngeal Carcinoma (NPC), is an highly chemo- and radiosensitive endemic malignancy in southeast Asia. More than one third of locally advanced cases relapse after curative treatment, especially because of bone, liver and lung metastases. Lymphocyte sub-populations favour EBV-associated carcinogenesis and tumour progression and several strategies aim to reverse this phenomenon. Receptor activator of NF-kB (RANK) and its Ligand (RANKL), key regulator of bone metabolisms, are expressed in several malignancies and tumor-infiltrating Tregs...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218366/haploidentical-natural-killer-cells-induce-remissions-in-non-hodgkin-lymphoma-patients-with-low-levels-of-immune-suppressor-cells
#7
Veronika Bachanova, Dhifaf Sarhan, Todd E DeFor, Sarah Cooley, Angela Panoskaltsis-Mortari, Bruce R Blazar, Julie M Curtsinger, Linda Burns, Daniel J Weisdorf, Jeffrey S Miller
We report a novel phase 2 clinical trial in patients with poor prognosis refractory non-Hodgkin lymphoma (NHL) testing the efficacy of haploidentical donor natural killer (NK) cell therapy (NK dose 0.5-3.27 × 107 NK cells/kg) with rituximab and IL-2 (clinicaltrials.gov NCT01181258). Therapy was tolerated without graft-versus-host disease, cytokine release syndrome, or neurotoxicity. Of 14 evaluable patients, 4 had objective responses (29%; 95% CI 12-55%) at 2 months: 2 had complete response lasting 3 and 9 months...
December 7, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29218244/exosomal-tgf-%C3%AE-1-is-correlated-with-lymphatic-metastasis-of-gastric-cancers
#8
Er-Yen Yen, Shi-Chuen Miaw, Jhang-Sian Yu, I-Rue Lai
Exosomes are nano-vesicles transporting bioactive material between cells. This study explored the prognostic association of exosomal TGF-β1 with lymph node (LN) metastasis of gastric cancer (GC). TGF-β1 expressions in the exosomes isolated from the gastroepiploic veins of 61 GC patients analyzed by ELISA. The regulatory T (Treg) cells in celiac LNs of gastric cancer analyzed by immunohistochemistry. Exosomal TGF-β1 expression and the ratio of Treg cells in draining LNs were both significantly associated with pathological stages and LN metastasis of gastric cancer...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29218110/downregulation-of-cathepsin-g-reduces-the-activation-of-cd4-t-cells-in-murine-autoimmune-diabetes
#9
Fang Zou, Xiaoyang Lai, Jing Li, Shuihong Lei, Lei Hu
Type 1 diabetes mellitus (T1DM) is an autoimmune disease due to progressive injury of islet cells mediated by T lymphocytes (T cells). Our previous studies have shown that only cathepsin G (CatG), not other proteases, is involved in the antigen presentation of proinsulin, and if the presentation is inhibited, the activation of CD4+ T cells induced by proinsulin is alleviated in T1DM patients, and CatG-specific inhibitor reduces the activation of CD4+ cells induced by proinsulin in T1DM patients. Therefore, we hypothesize that CatG may play an important role in the activation of CD4+ T cells in T1DM...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29218089/the-role-of-sildenafil-in-the-development-of-transplant-arteriosclerosis-in-rat-aortic-grafts
#10
Shuai Luo, Mei Yang, Hao Jin, Zi-Qiang Xu, Yi-Fu Li, Peng Xia, Yi-Rrong Yang, Bi-Cheng Chen, Yan Zhang
Chronic rejection (CR), which is characterized histologically by progressive graft arteriosclerosis, remains a significant barrier to the long-term survival of a graft. Sildenafil has been shown to protect vascular endothelial cells. In this study, we found that sildenafil significantly reduces the thickness of transplant vascular intima in a rat aortic transplant model. Moreover, sildenafil dramatically decreased the expression of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and α-smooth muscle actin (α-SMA) in the grafted aortas and increased the concentrations of cyclic guanosine monophosphate (cGMP) and endothelial nitric oxide synthase (eNOS) in serum...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29216911/dynamic-expression-of-cytokine-and-transcription-factor-genes-during-experimental-fasciola-gigantica-infection-in-buffaloes
#11
Wei Shi, Zhi-Yong Wei, Hany M Elsheikha, Fu-Kai Zhang, Zhao-An Sheng, Ke-Jing Lu, Dong-Ying Wang, Wei-Yi Huang, Xing-Quan Zhu
BACKGROUND: Determining the mechanisms involved in the immune-pathogenesis of the tropical liver fluke, Fasciola gigantica, is crucial to the development of any effective therapeutic intervention. Here, we examined the differential gene expression of cytokines and transcription factors in the liver of F. gigantica-infected buffaloes, over the course of infection. METHODS: Water buffaloes (swamp type) were infected orally with 500 F. gigantica encysted metacercariae...
December 8, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29213216/tumor-infiltrating-cd4-t-cells-in-patients-with-gastric-cancer
#12
Long Yuan, Benling Xu, Peng Yuan, Jinxue Zhou, Peng Qin, Lu Han, Guangyu Chen, Zhenlei Wang, Zengci Run, Peng Zhao, Quanli Gao
Background: T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4+ T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients. Materials and methods: Patients with GC diagnosed on the basis of pre-operative staging and laparotomy findings were approached for enrollment between 2014 and 2015 at the Affiliated Cancer Hospital of Zhengzhou University, China...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29213081/pak2-is-essential-for-the-function-of-foxp3-regulatory-t-cells-through-maintaining-a-suppressive-treg-phenotype
#13
Kyle L O'Hagan, Stephen D Miller, Hyewon Phee
Foxp3, a key transcription factor that drives lineage differentiation of regulatory T cells (Tregs), was thought to imprint a unique and irreversible genetic signature within Tregs. Recent evidence, however, suggests that loss or attenuation of Foxp3 expression can cause Tregs to de-differentiate into effector T cells capable of producing proinflammatory cytokines. Herein, we report that the signaling kinase, p21-activated kinase 2 (Pak2), is essential for maintaining Treg stability and suppressive function...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212947/requirement-of-treg-intrinsic-ctla4-pkc%C3%AE-signaling-pathway-for-suppressing-tumor-immunity
#14
Christophe Pedros, Ann J Canonigo-Balancio, Kok-Fai Kong, Amnon Altman
The ability of Tregs to control the development of immune responses is essential for maintaining immune system homeostasis. However, Tregs also inhibit the development of efficient antitumor responses. Here, we explored the characteristics and mechanistic basis of the Treg-intrinsic CTLA4/PKCη signaling pathway that we recently found to be required for contact-dependent Treg-mediated suppression. We show that PKCη is required for the Treg-mediated suppression of tumor immunity in vivo. The presence of PKCη-deficient (Prkch-/-) Tregs in the tumor microenvironment was associated with a significantly increased expression of the costimulatory molecule CD86 on intratumoral CD103+ DCs, enhanced priming of antigen-specific CD8+ T cells, and greater levels of effector cytokines produced by these cells...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29212449/maternal-variant-in-the-upstream-of-foxp3-gene-on-the-x-chromosome-is-associated-with-recurrent-infertility-in-japanese-black-cattle
#15
Taichi Arishima, Shinji Sasaki, Tomohiro Isobe, Yoshihisa Ikebata, Shinichi Shimbara, Shogo Ikeda, Keisuke Kawashima, Yutaka Suzuki, Manabu Watanabe, Sumio Sugano, Kazunori Mizoshita, Yoshikazu Sugimoto
BACKGROUND: Repeat breeding, which is defined as cattle failure to conceive after three or more inseminations in the absence of clinical abnormalities, is a substantial problem in cattle breeding. To identify maternal genetic variants of repeat breeding in Japanese Black cattle, we selected 29 repeat-breeding heifers that failed to conceive following embryo transfer (ET) and conducted a genome-wide association study (GWAS) using the traits. RESULTS: We found that a single-nucleotide polymorphism (SNP; g...
December 6, 2017: BMC Genetics
https://www.readbyqxmd.com/read/29212384/articular-and-subcutaneous-adipose-tissues-of-rheumatoid-arthritis-patients-represent-equal-sources-of-immunoregulatory-mesenchymal-stem-cells
#16
Urszula Skalska, Ewa Kuca-Warnawin, Anna Kornatka, Iwona Janicka, Urszula Musiałowicz, Tomasz Burakowski, Ewa Kontny
Adipose-derived mesenchymal stem cells (ASCs) have immunoregulatory properties, but their activity is dependent on signals provided by the local microenvironment. It is likely that highly inflammatory milieu of rheumatoid joint affects ASCs activity. To test this hypothesis, the function of rheumatoid ASCs derived from articular adipose tissue (AT-ASCs) and ASCs derived from subcutaneous adipose tissue (Sc-ASCs) has been analysed. Articular adipose tissue (infrapatellar fat pad) and subcutaneous adipose tissue (from the site of skin closure with sutures) were obtained from rheumatoid arthritis (RA) patients undergoing total knee joint replacement surgery...
December 6, 2017: Autoimmunity
https://www.readbyqxmd.com/read/29211935/a-simple-twist-of-phosphate-immunological-synapse-formation-and-t-cell-receptor-signaling-outcome-in-regulatory-t-cells
#17
Talal A Chatila, Raffaele De Palma
Signaling through the T cell receptor (TCR) regulates T cell homeostasis and effector functions. However, a full accounting of the TCR-coupled signaling networks and how their interplay determines specific functional outcomes remains elusive. Of particular interest are efforts over the last years to elucidate distinctive features of TCR signaling in regulatory T cells (Treg) that may account for some of their unique functional attributes as compared to conventional T (Tconv) cells. In this issue of the European Journal of Immunology, van Ham et al...
December 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29211912/intestinal-t-cell-profiling-in-inflammatory-bowel-disease-linking-t-cell-subsets-to-disease-activity-and-disease-course
#18
Carolijn Smids, Carmen S Horjus Talabur Horje, Julia Drylewicz, Britt Roosenboom, Marcel J M Groenen, Elly van Koolwijk, Ellen G van Lochem, Peter J Wahab
Introduction: A dysregulated intestinal T-cell response is presumed in patients with Inflammatory Bowel Disease (IBD). In this longitudinal study, we investigated the changes in intestinal T lymphocyte subsets in IBD at first presentation and over time during endoscopic active or inactive disease and relate them to disease activity and outcome. Material & method: We included 129 newly diagnosed patients (87 Crohn´s Disease (CD), 42 ulcerative colitis (UC)) and 19 healthy controls (HC)...
December 4, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29211057/neonatal-neutrophils-stimulated-by-group-b-streptococcus-induce-a-proinflammatory-t-helper-cell-bias
#19
Jianguo Lin, Seema Haridas, Stephen J Barenkamp, Larissa Chioquetta Lorenset, Ashley Sang Eun Lee, Benjamin T Schroeder, Guangyong Peng, Joyce M Koenig
BackgroundGroup B Streptococcus (GBS) infection causes inflammatory comorbidities in newborns. While the mechanisms remain unclear, evidence suggests that impaired innate-adaptive immune interactions may be contributory. We hypothesized that GBS-stimulated neonatal neutrophils provide a milieu that may drive proinflammatory T-helper (Th) cell programming.MethodsNeutrophils were stimulated with Type III GBS (COH1); supernatants or intact neutrophils were cocultured with CD4+ T cells or regulatory T cells (Tregs)...
December 6, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29210727/regulatory-t-cells-from-the-bench-to-the-clinic-and-back
#20
Basmah S Al Dulaijan, Amr Mansouri, Jordan Karnyski, Jamil Azzi
PURPOSE OF REVIEW: The main objective of this review is to briefly highlight how we gradually came to understand regulatory T cells (Tregs) and forkhead box p3 (FoxP3) biology, including their function and regulation. We will also discuss how this knowledge is being translated into the clinical setting and the significant challenges that need to be overcome. RECENT FINDINGS: CD4FoxP3 Tregs are key players in immune regulation. Their deficiency and dysfunction have been implicated in the pathogenesis of many autoimmune diseases...
November 27, 2017: Current Opinion in Organ Transplantation
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