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https://www.readbyqxmd.com/read/28820075/t-regulatory-cell-subsets-in-children-with-type-1-diabetes-mellitus-relation-to-control-of-the-disease
#1
Mabrouk Ghonaim, Rawhia El-Edel, Wafaa Abo El Fotoh, Samar Kamal Eldein, Samar Salman
BACKGROUND: Type 1 diabetes mellitus described as a chronic metabolic disorder characterized by aggressive immune β-cell destruction. There are numbers of varied immune mechanisms for sustaining self-tolerance in opposition to the autoimmune disorders. A recessive tolerance accomplished by thymic gland via a negative assortment of different clones while a dominant tolerance accomplished by the regulatory T cells (Treg) in the periphery. Treg (CD4+CD25+FOXP3+) are subsets of T cells which have an essential role in maintaining tolerance...
August 17, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28820073/immunomodulatory-role-of-arsenic-on-regulatory-t-cells
#2
Rizwanul Haque, Archana Chaudhary, Nadra Sadaf
Background and objective-Chronic Arsenic (As) exposure continued to be a cause of major problem associated with different kind of diseases including skin problem and different types of cancer. As exposure leads to numerous other pathological conditions that affect millions of people worldwide on a regular basis. It was recently established that As toxicity affects immune system and modulate the function and survival of cells involved in immune regulation. Arsenic trioxide (As2O3) was reported to be an effective apoptosis inducer in a variety of cell types...
August 17, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28819402/pd-l1-expression-is-associated-with-foxp3-regulatory-t-cell-infiltration-of-soft-tissue-sarcoma-and-poor-patient-prognosis
#3
Yi Que, Wei Xiao, Yuan-Xiang Guan, Yao Liang, Shu-Mei Yan, Huo-Ying Chen, Qiao-Qiao Li, Bu-Shu Xu, Zhi-Wei Zhou, Xing Zhang
Background: Programmed death ligand-1(PD-L1) functions as a negative mediator of immune response through different pathways in anti-tumor immunity. Recent studies have reported that PD-L1 plays a pivotal role in the function of regulatory T-cells (Tregs). Although increases in FOXP3+ Tregs infiltration and PD-L1 expression have been revealed in several cancers, their correlation with soft tissue sarcoma remains unknown. Methods: We included 163 cases of soft tissue sarcoma who were diagnosed and underwent extensive and radical resection at the Sun Yat-sen University Cancer Center, Guangzhou, China, from 2000-2010...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819166/histone-protein-deacetylase-11-targeting-promotes-foxp3-treg-function
#4
Jianbing Huang, Liqing Wang, Satinder Dahiya, Ulf H Beier, Rongxiang Han, Arabinda Samanta, Joel Bergman, Eduardo M Sotomayor, Edward Seto, Alan P Kozikowski, Wayne W Hancock
Current interest in Foxp3+ T-regulatory (Treg) cells as therapeutic targets in transplantation is largely focused on their harvesting pre-transplant, expansion and infusion post-transplantation. An alternate strategy of pharmacologic modulation of Treg function using histone/protein deacetylase inhibitors (HDACi) may allow more titratable and longer-term dosing. However, the effects of broadly acting HDACi vary, such that HDAC isoform-selective targeting is likely required. We report data from mice with constitutive or conditional deletion of HDAC11 within Foxp3+ Treg cells, and their use, along with small molecule HDAC11 inhibitors, in allograft models...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819022/%C3%AE-adrenergic-signaling-in-mice-housed-at-standard-temperatures-suppresses-an-effector-phenotype-in-cd8-t-cells-and-undermines-checkpoint-inhibitor-therapy
#5
Mark J Bucsek, Guanxi Qiao, Cameron R MacDonald, Thejaswini Giridharan, Lauren Evans, Brian Niedzwecki, Haichao Liu, Kathleen M Kokolus, Jason W-L Eng, Michelle N Messmer, Kristopher Attwood, Scott I Abrams, Bonnie L Hylander, Elizabeth A Repasky
The immune context of tumors has significant prognostic value and is predictive of responsiveness to several forms of therapy, including immunotherapy. We report here that CD8(+) T cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies - physiologic (manipulation of ambient thermal environment), pharmacologic (β-blockers), and genetic (β2-adrenergic receptor knockout mice) to reduce adrenergic stress signaling in two widely studied preclinical mouse tumor models...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28817385/novel-molecular-defects-associated-with-very-early-onset-inflammatory-bowel
#6
Sara Ciullini Mannurita, Eleonora Gambineri
PURPOSE OF REVIEW: Immune dysregulation disorders present with common clinical features of multiorgan autoimmunity. Gastrointestinal involvement is the hallmark of an impaired immune homeostasis. This review will give an overview on the novel phenotypes, highlighting the major points that will help to enable early diagnosis and treatment. RECENT FINDINGS: The rapid progress on DNA sequencing technologies have led to the identification of monogenic defects that adversely impact the control of immune homeostasis...
August 16, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#7
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#8
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28815044/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#9
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/28814673/human-lung-tumor-foxp-tregs-upregulate-four-treg-locking-transcription-factors
#10
Tatiana Akimova, Tianyi Zhang, Dmitri Negorev, Sunil Singhal, Jason Stadanlick, Abhishek Rao, Michael Annunziata, Matthew H Levine, Ulf H Beier, Joshua M Diamond, Jason D Christie, Steven M Albelda, Evgeniy B Eruslanov, Wayne W Hancock
Experimental data indicate that FOXP3+ Tregs can markedly curtail host antitumor immune responses, but the properties of human intratumoral Tregs are still largely unknown, in part due to significant methodologic problems. We studied the phenotypic, functional, epigenetic, and transcriptional features of Tregs in 92 patients with non-small-cell lung cancer, comparing the features of Tregs within tumors versus corresponding blood, lung, and lymph node samples. Intratumoral Treg numbers and suppressive function were significantly increased compared with all other sites but did not display a distinctive phenotype by flow cytometry...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28813651/a-rogue-foxp3-mutant-undermines-treg-cell-function
#11
Ye Zheng
Hayatsu et al. (2017) reveal that a FOXP3 mutant found in some patients afflicted with the autoimmune disease IPEX has broadened DNA-recognition specificity, directly repressing the expression of the gene encoding the transcription factor Batf. Their findings identify Batf as critical to tissue regulatory T cell function and suggest that polymorphisms that impact FOXP3 DNA-binding specificity may contribute susceptibility to autoimmune disease.
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28811236/interleukin-26-is-overexpressed-in-beh%C3%A3-et-s-disease-and-enhances-th17-related-cytokines
#12
Wajih Kaabachi, Eya Bouali, Anissa Berraïes, Imen Ben Dhifallh, Besma Hamdi, Kamel Hamzaoui, Agnès Hamzaoui
Behçet's disease (BD) is a multi-systemic inflammatory disorder characterized by the "triple symptom complex". Several pro-inflammatory cytokines, mainly derived from the immune Th17 axis, seem to be involved in different pathogenic pathways leading to development of the clinical manifestations. Here, we have analyzed the expression and role of IL-26 in active BD patients, an inflammatory disorder characterized by bronchoalveolar lavage fluid (BAL) and in cerebrospinal fluid (CSF) inflammation. On this basis, the primary aim of our work was to study IL-26 levels in serum, BAL CSF) from active BD patients...
August 12, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28811075/regulatory-t-cell-deficient-scurfy-mice-exhibit-a-th2-m2-like-inflammatory-response-in-the-skin
#13
Stefanie Haeberle, Verena Raker, Jessica Haub, Yong O Kim, Shih-Yen Weng, Osman K Yilmaz, Alexander Enk, Kerstin Steinbrink, Detlef Schuppan, Eva N Hadaschik
BACKGROUND: Scurfy mice have a functional defect in regulatory T cells (Treg), which leads to lethal multi-organ inflammation. The missing Treg function results in uncontrolled autoimmune cellular and humoral inflammatory responses. We and others have previously shown that during the course of disease scurfy mice develop severe skin inflammation and autoantibodies including anti-nuclear autoantibodies (ANA). OBJECTIVE: Autoimmune skin inflammation and ANA are hallmarks for the diagnosis of autoimmune connective tissue diseases; therefore we analyzed scurfy mice for typical signs of these diseases...
July 13, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28810565/alteration-of-th17-and-foxp3-regulatory-t-cells-in-patients-with-unexplained-recurrent-spontaneous-abortion-before-and-after-the-therapy-of-hcg-combined-with-immunoglobulin
#14
Jing Sha, Fumin Liu, Jingfang Zhai, Xiaoyun Liu, Qinglin Zhang, Bei Zhang
We conducted this study to investigate the effects of the combination therapy of human chorionic gonadotropin (hCG) plus immunoglobulin (IG) on the levels of T helper 17 (Th17) cells and Foxp3(+) regulatory T cells (Treg) in patients with unexplained recurrent spontaneous abortion (URSA). Twenty pregnant women with URSA underwent combination therapy of hCG plus IG. Flow cytometry was performed to measure the proportions of Th17 and Treg cells before and after treatment. RT-PCR and ELISA were applied to detect the concentrations of interleukin (IL)-17, IL-6, IL-10, and transforming growth factor (TGF)-β1 in the peripheral blood...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810531/mir-146a-overexpression-effectively-improves-experimental-allergic-conjunctivitis-through-regulating-cd4-cd25-t-cells
#15
Yang Yang, Xiaolong Yin, Jinglin Yi, Xiaowei Peng
OBJECTIVE: To study the mechanism of miR-146a in the regulation of allergic conjunctivitis (AC) through CD4(+)CD25(-)T cells. METHODS: BALB/c mice were sensitized with ragweed pollen (RW) and alum, and then challenged with RW. Eosinophil infiltration was determined using Giemsa assay. ELISA assay was performed to examine the level of antigen-specific IgE in the serum and cytokine levels in splenocytes. The expression of miR-146a was measured by qRT-PCR. Flow cytometric analysis was used to analyze the percentage of CD4(+)CD25(-)T cells and Tregs...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28809557/in-silico-and-in-vitro-interactions-between-short-chain-fatty-acids-and-human-histone-deacetylases
#16
Rou Hui Ho, James Chun Yip Chan, Hao Fan, Dorinda Yan Qin Kioh, Bee Wah Lee, Eric Chun Yong Chan
Short chain fatty acids (SCFAs) are postulated to modulate the immune development of neonates via epigenetic regulations such as histone deacetylase (HDAC) inhibition. In the context of atopic diseases, the inhibition of HDAC maintains T-cell homeostasis and induces naïve T-cell differentiation into adaptive Treg, which regulates the production of anti-inflammatory cytokines and suppression of Th2 immune responses. We investigated the structure-inhibition relationships of SCFAs with class I HDAC3 and class IIa HDAC7 using in silico docking simulation and in vitro human recombinant HDAC inhibition assay...
August 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28808862/a-pilot-study-comparing-t-regulatory-cell-function-among-healthy-children-in-different-areas-of-gansu-china
#17
Panhong Gou, Xiaoru Chang, Zhonghui Ye, Yueli Yao, Patton Khuu Nguyen, Sally Katharine Hammond, Junling Wang, Sa Liu
Immune system is critical to protecting human health from toxic substances. Our previously published research had found an important link between polycyclic aromatic hydrocarbons (PAHs) in ambient air and changes at the DNA level in immune cells that led to impaired function of regulatory T (Treg) cells in children living in California, USA. But molecular and cellular pathways of these changes remain unclear. The present study aims to explore whether exposure to PAHs leads to changes in Treg cells functions of children living in Gansu, China, where ambient air pollution levels are much higher than those in California, and to explore potential mechanisms of PAH-induced immunological dysfunctions...
August 14, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#18
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28807569/il-10-engineered-human-cd4-tr1-cells-eliminate-myeloid-leukemia-in-an-hla-class-i-dependent-mechanism
#19
Grazia Locafaro, Grazia Andolfi, Fabio Russo, Luca Cesana, Antonello Spinelli, Barbara Camisa, Fabio Ciceri, Angelo Lombardo, Attilio Bondanza, Maria Grazia Roncarolo, Silvia Gregori
T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4(+) T cells into T regulatory type 1 (Tr1)-like (CD4(IL-10)) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models...
July 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28807496/cd4-effector-t-cell-differentiation-is-controlled-by-il-15-that-is-expressed-and-presented-in-trans
#20
Adam T Waickman, Davinna L Ligons, SuJin Hwang, Joo-Young Park, Vanja Lazarevic, Noriko Sato, Changwan Hong, Jung-Hyun Park
T cells are both producers and consumers of cytokines, and autocrine cytokine signaling plays a critical role in T cell immunity. IL-15 is a homeostatic cytokine for T cells that also controls inflammatory immune responses. An autocrine role of T cell-derived IL-15, however, remains unclear. Here we examined IL-15 expression and signaling upon effector T cell differentiation in mice, and, surprisingly, found that CD4 T cells did not express IL-15. CD4 T cells lacked Il15 gene reporter activity, did not contain IL-15 transcripts, and did not produce IL-15Rα, the proprietary IL-15 receptor required for IL-15 trans-presentation...
August 11, 2017: Cytokine
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