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https://www.readbyqxmd.com/read/29665497/the-effects-of-resiquimod-in-an-ovalbumin-induced-allergic-rhinitis-model
#1
Shenhong Qu, Taijie Qin, Min Li, Shaojie Zhang, Linsong Ye, Jiazhang Wei, Hua Fan, Baiwen Chen
Growing evidence indicates that the Toll-like receptor7/8(TLR7/8) agonist resiquimod (R848) is a potential inhibitor of type-2 immunity. However, the mechanisms mediating its therapeutic effects are not fully understood. This study investigated the effects of R848 on OVA-induced allergic rhinitis(AR) mice and the expression of IL-25, IL-33, TSLP, T-cell immunoglobulin mucin1 (TIM1) and T-cell immunoglobulin mucin3 (TIM3). BALB/c mice were intranasally sensitized and challenged with ovalbumin (OVA), and R848 was intraperitoneally injected into AR mice...
April 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#2
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella M M Eppenberger-Castori, Luigi Terracciano, Micha Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
PURPOSE: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. EXPERIMENTAL DESIGN: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29657243/distinct-pattern-of-th17-treg-cells-in-pregnant-women-with-a-history-of-unexplained-recurrent-spontaneous-abortion
#3
Jinfeng Qian, Na Zhang, Jing Lin, Caiyan Wang, Xinyao Pan, Lanting Chen, Dajin Li, Ling Wang
The aim of the current study was to determine the pattern of immune cells and related functional molecules in peripheral blood and at the maternal-fetal interface in women with unexplained recurrent spontaneous abortion (URSA). In part I, 155 women were included and divided into four groups: non-pregnant controls with no history of URSA (NPCs), pregnant controls with no history of URSA (PCs), non-pregnant women with a history of URSA (NPUs), and pregnant women with a history of URSA (PUs). Venous blood samples were collected and analyzed...
April 15, 2018: Bioscience Trends
https://www.readbyqxmd.com/read/29651443/immature-dendritic-cell-therapy-confers-durable-immune-modulation-in-an-antigen-dependent-and-antigen-independent-manner-in-nonobese-diabetic-mice
#4
Jeannette Lo, Chang-Qing Xia, Ruihua Peng, Michael J Clare-Salzler
Dendritic cell (DC) immunotherapy has been effective for prevention of type 1 diabetes (T1D) in NOD mice but fails to protect if initiated after active autoimmunity. As autoreactivity expands inter- and intramolecularly during disease progression, we investigated whether DCs unpulsed or pulsed with β cell antigenic dominant determinants (DD), subdominant determinants (SD), and ignored determinants (ID) could prevent T1D in mice with advanced insulitis. We found that diabetes was significantly delayed by DC therapy...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29651287/neutralizing-anti-cytokine-autoantibodies-against-interferon-%C3%AE-in-immunodysregulation-polyendocrinopathy-enteropathy-x-linked
#5
Jacob M Rosenberg, Maria E Maccari, Federica Barzaghi, Eric J Allenspach, Claudio Pignata, Giovanna Weber, Troy R Torgerson, Paul J Utz, Rosa Bacchetta
Anti-cytokine autoantibodies (ACAAs) have been described in a growing number of primary immunodeficiencies with autoimmune features, including autoimmune polyendocrine syndrome type I (APS-1), a prototypical disease of defective T cell-mediated central tolerance. Whether defects in peripheral tolerance lead to similar ACAAs is unknown. Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) is caused by mutations in FOXP3 , a master regulator of T regulatory cells (Treg ), and consequently results in defective T cell-mediated peripheral tolerance...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29648813/small-molecule-neuropilin-1-antagonists-combine-anti-angiogenic-and-anti-tumour-activity-with-immune-modulation-through-reduction-of-transforming-growth-factor-beta-tgf%C3%AE-production-in-regulatory-t-cells
#6
Jonathan Powell, Filipa Mota, David Steadman, Christelle Soudy, Jeremy T Miyauchi, Stuart Crosby, Ashley Jarvis, Tifelle Reisinge, Natalie Winfield, Graham Evans, Aled Finniear, Tamas Yelland, Yi-Tai Chou, A W Edith Chan, Andrew O'Leary, Lili Cheng, Dan Liu, Ntina Fotinou, Carla Milagre, John F Martin, Haiyan Jia, Paul Frankel, Snezana Djordjevic, Stella E Tsirka, Ian C Zachary, David L Selwood
We report the design, synthesis and comprehensive studybiological evaluation of a range ofsome potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune response to tumours, particularly in Treg cell fragility, required for PD1 checkpoint blockade. The design of these compounds was based on a previously identified compound EG00229, EG00229 which was used a starting point for optimisation. Through targeting of specific amino-acid residues additional H-bonding interactions were introduced, which led to increases in binding affinity and potency...
April 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29628925/human-endothelial-cells-modulate-cd4-t-cell-populations-and-enhance-regulatory-t-cell-suppressive-capacity
#7
Wen Chean Lim, Michael Olding, Eugene Healy, Timothy M Millar
Endothelial cells (ECs) line the luminal surface of blood vessels and have an active role in the recruitment of leukocytes, including immune cell activation. Regulatory T cells (Tregs) are immune suppressor cells that maintain peripheral tolerance and must interact with the endothelium as they traffic into tissue. We hypothesized that human ECs could modulate Tregs and their suppressor function. Cocultures of CD4+ T cells with human umbilical vein ECs (HUVECs) or dermal microvascular ECs (HDMECs) were conducted and analyzed for activation and proliferation after 72 and 120 h using flow cytometry...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29627063/high-fiber-dietary-and-sodium-butyrate-attenuate-experimental-autoimmune-hepatitis-through-regulation-of-immune-regulatory-cells-and-intestinal-barrier
#8
En-De Hu, Da-Zhi Chen, Jin-Lu Wu, Feng-Bin Lu, Lu Chen, Ming-Hua Zheng, Hui Li, Yu Huang, Ji Li, Xiao-Ya Jin, Yue-Wen Gong, Zhuo Lin, Xiao-Dong Wang, Lan-Man Xu, Yong-Ping Chen
Autoimmune hepatitis (AIH) is chronic autoimmune liver disease accompanied with the imbalance of Treg/Th17 and increased intestinal permeability. We investigated the effects of a high fiber diet and sodium butyrate on the Treg/Th17 and intestinal barrier function in an experimental autoimmune hepatitis. Intraperitoneal injection of hepatic antigen (S100) was used to induce experimental autoimmune hepatitis mice model and mice were divided into normal control, S100 model control, S100 plus high fiber diet and S100 plus sodium butyrate...
March 22, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29626602/protective-properties-of-combined-fungal-polysaccharides-from-cordyceps-sinensis-and-ganoderma-atrum-on-colon-immune-dysfunction
#9
Song-Tao Fan, Shao-Ping Nie, Xiao-Jun Huang, Sunan Wang, Jie-Lun Hu, Jun-Hua Xie, Qi-Xing Nie, Ming-Yong Xie
In vivo an ecological network of polysaccharides utilization by gut microbiota is not only an intense competition but also an impressive cooperation pattern. The present study evaluated the in vivo protective effect of combined fungal polysaccharides (CFP) from Cordyceps sinensis and Ganoderma atrum on colon immune dysfunction, induced by 150 mg/kg cyclophosphamide (CP). The results showed that C. sinensis polysaccharides (CSP) significantly promoted microbial-derived butyrate to improve histone h3 acetylation mediating regulatory T (Treg) cell specific Foxp3, as well as significantly restored CP-induced elevation of interleukin (IL)-17 and IL-21...
April 4, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29625390/dysfunction-of-regulatory-t-cells-in-patients-with-ankylosing-spondylitis-is-associated-with-a-loss-of-tim-3
#10
Mingfei Wang, Chengyi Liu, Allen Bond, Jun Yang, Xu Zhou, Jian Wang, Bin Ji
An expansion of regulatory T cells (Tregs) in ankylosing spondylitis (AS) was observed. However, AS patients continue to exhibit aberrant inflammation. In this study, we collected PBMCs from 26 AS patients and 26 healthy controls, and investigated the functional capacity of Treg cells from these subjects. In AS patients, the frequency of CD4+ CD25+ Foxp3+ CD127- Treg cells was slightly increased compared to healthy controls, but the level of Foxp3 MFI in AS patient CD4+ CD25+ Foxp3+ CD127- Treg cells was significantly lower than that in healthy control CD4+ CD25+ Foxp3+ CD127- Treg cells...
April 2, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29625181/hyaluronan-in-immune-dysregulation-and-autoimmune-diseases
#11
REVIEW
Nadine Nagy, Hedwich F Kuipers, Payton L Marshall, Esther Wang, Gernot Kaber, Paul L Bollyky
The tissue microenvironment contributes to local immunity and to the pathogenesis of autoimmune diseases - a diverse set of conditions characterized by sterile inflammation, immunity against self-antigens, and destruction of tissues. However, the specific factors within the tissue microenvironment that contribute to local immune dysregulation in autoimmunity are poorly understood. One particular tissue component implicated in multiple autoimmune diseases is hyaluronan (HA), an extracellular matrix (ECM) polymer...
April 3, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29623079/the-significance-of-tumor-necrosis-factor-receptor-type-ii-in-cd8-regulatory-t-cells-and-cd8-effector-t-cells
#12
REVIEW
Lin-Lin Ye, Xiao-Shan Wei, Min Zhang, Yi-Ran Niu, Qiong Zhou
Tumor necrosis factor (TNF) is a pleiotropic cytokine that has both pro-inflammatory and anti-inflammatory functions. The biological functions of TNF are mediated by two receptors, TNF receptor type I (TNFR1) and TNF receptor type II (TNFR2). TNFR1 is expressed universally on almost all cell types and has been extensively studied, whereas TNFR2 is mainly restricted to immune cells and some tumor cells and its role is far from clarified. Studies have shown that TNFR2 mediates the stimulatory activity of TNF on CD4+ Foxp3+ regulatory T cells (Tregs) and CD8+ Foxp3+ Tregs, and is involved in the phenotypic stability, proliferation, activation, and suppressive activity of Tregs...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29622483/mesenchymal-stromal-cell-exosome-enhanced-regulatory-t-cell-production-through-an-antigen-presenting-cell-mediated-pathway
#13
Bin Zhang, Ronne Wee Yeh Yeo, Ruenn Chai Lai, Eugene Wei Kian Sim, Keh Chuang Chin, Sai Kiang Lim
BACKGROUND AIMS: The immunomodulatory property of mesenchymal stromal cell (MSC) exosomes is well documented. On the basis of our previous report that MSC exosomes increased regulatory T-cell (Treg) production in mice with allogenic skin graft but not in ungrafted mice, we hypothesize that an activated immune system is key to exosome-mediated Treg production. METHODS: To test our hypothesis, MSC exosomes were incubated with mouse spleen CD4+ T cells that were activated with either anti-CD3/CD28 mAbs or allogenic antigen-presenting cell (APC)-enriched spleen CD11c+ cells to determine whether production of mouse CD4+ CD25+ T cells or CD4+ CD25+ Foxp3+ Tregs could be induced...
April 2, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29621784/exosomes-derived-from-dendritic-cells-attenuate-liver-injury-by-modulating-the-balance-of-treg-and-th17-cells-after-ischemia-reperfusion
#14
Lei Zheng, Zhi Li, Wei Ling, Deming Zhu, Zhiwen Feng, Lianbao Kong
BACKGROUND/AIMS: The present study aimed to evaluate the effects as well as the underlying mechanisms of bone marrow-derived dendritic cells (BMDCs) and exosomes produced by BMDCs (DEXs) on hepatic ischemia-reperfusion (I/R) injury (IRI). METHODS: Primary hepatocytes were isolated and used to mimic the liver IR microenvironment. BMDCs were induced and characterized both biochemically with a flow cytometer (FCM) and biophysically with a microscope. Then, we exposed BMDCs to the supernatants from primary hepatocytes and evaluated the maturation of BMDCs by FCM...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29621426/tumor-infiltrating-treg-mdsc-and-ido-expression-associated-with-outcomes-of-neoadjuvant-chemotherapy-of-breast-cancer
#15
Fangxuan Li, Yang Zhao, Lijuan Wei, Shixia Li, Juntian Liu
BACKGROUND: Regulatory T cells(Tregs) and myeloid-derived suppressor cells(MDSCs) represent two immunosuppressive cell populations that are important in the establishment and maintenance of cancer immune tolerance. MDSCs can express IDO and promote immune tolerance via expansion of Treg cell. METHOD: We use needle biopsy breast cancer tissues prior to neoadjuvant chemotherapy(NCT) staining for CD33, Foxp3 and IDO by immunohistochemistry to evaluate whether they were correlated with subsequent treatment responses in breast cancer...
April 5, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29620246/roseburia-intestinalis-inhibits-interleukin%C3%A2-17-excretion-and-promotes-regulatory-t-cells-differentiation-in-colitis
#16
Changxin Zhu, Kerui Song, Zhaohua Shen, Yongsheng Quan, Bei Tan, Weiwei Luo, Shuai Wu, Kai Tang, Zhenyu Yang, Xiaoyan Wang
Roseburia intestinalis (R. intestinalis) is one of the dominant intestinal bacterial microbiota and is decreased in patients with inflammatory bowel disease (IBD). It helps protect colonic mucosa against the development of inflammation and subsequent IBD, however its underlying mechanisms are unclear. The aim of the present study was to evaluate the anti‑inflammatory properties of R. intestinalis in vitro and in an animal model of IBD. The effects of R. intestinalis on disease activity index (DAI) scores, intestinal pathology, the expression of interleukin (IL)‑17 and the frequency of CD4+CD25+Foxp3+ regulatory T cells (Treg) were evaluated in vivo in a model of 2,4,6‑trinitrobenzenesulfonic acid solution (TNBS)‑induced colitis...
March 29, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29619880/low-dose-il-2-expands-cd4-regulatory-t-cells-with-a-suppressive-function-in-vitro-via-the-stat5-dependent-pathway-in-patients-with-chronic-kidney-diseases
#17
Yuanyuan Li, Xueyong Liu, Wei Wang, Shaohua Wang, Jianchun Zhang, Song Jiang, Yang Wang, Liping Li, Jinghua Li, Youkang Zhang, Haichang Huang
BACKGROUND: Patients with chronic kidney disease (CKD) often have CD4+ regulatory T cells (Tregs) dysfunction and chronic inflammation. We aim to investigate the effect, function, and related mechanism of low-dose IL-2 on CD4+ regulatory T cells expansion in vitro from patients with CKD. METHODS: A total of 148 newly diagnosed patients with CKD at Stage III and 35 healthy volunteer subjects were recruited into our studies. The number of peripheral Tregs in peripheral blood mononuclear cells isolated from CKD patients, which were characterized by FACS as CD4+ CD25hi and CD4+ CD25+ FoxP3+ ...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29619420/changes-in-natural-killer-cells-and-exhausted-memory-regulatory-t-cells-with-corticosteroid-therapy-in-acute-autoimmune-hepatitis
#18
Hannah C Jeffery, Manjit K Braitch, Chris Bagnall, James Hodson, Louisa E Jeffery, Rebecca E Wawman, Lin Lee Wong, Jane Birtwistle, Helen Bartlett, Ansgar W Lohse, Gideon M Hirschfield, Jessica Dyson, David Jones, Stefan G Hubscher, Paul Klenerman, David H Adams, Ye H Oo
Autoimmune hepatitis (AIH) is an immune-mediated liver disease currently treated by immunosuppressive medications with significant side effects. Thus, novel mechanistic treatments are greatly needed. We performed prospective deep immunophenotyping of blood immune cells in patients with acute AIH before and after corticosteroid therapy. Blood samples from 26 patients with acute AIH (United Kingdom-AIH Consortium) were phenotyped by flow cytometry at baseline and 4 months after starting corticosteroids. Pretreatment liver tissues were stained for forkhead box P3-positive (FOXP3POS ) regulatory T cells (Tregs), clusters of differentiation (CD)56POS natural killer (NK) cells, and chemokine (C-X-C motif) ligand 10...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29619032/an-autocrine-tnf%C3%AE-tumor-necrosis-factor-receptor-2-loop-promotes-epigenetic-effects-inducing-human-treg-stability-in-vitro
#19
Paulo C M Urbano, Hans J P M Koenen, Irma Joosten, Xuehui He
A crucial issue for Treg-based immunotherapy is to maintain a bona fide Treg phenotype as well as suppressive function during and after ex vivo expansion. Several strategies have been applied to harness Treg lineage stability. For instance, CD28 superagonist stimulation in vitro , in the absence of CD3 ligation, is more efficient in promoting Treg proliferation, and prevention of pro-inflammatory cytokine expression, such as IL-17, as compared to CD3/CD28-stimulated Treg. Addition of the mTOR inhibitor rapamycin to Treg cultures enhances FOXP3 expression and Treg stability, but does impair proliferative capacity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29618596/alternative-splicing-of-foxp3-controls-regulatory-t-cell-effector-functions-and-is-associated-with-human-atherosclerotic-plaque-stability
#20
Anne-Laure Joly, Christina Seitz, Sang Liu, Nikolai V Kouznetsov, Karl Gertow, Lisa S Westerberg, Gabrielle Paulsson-Berne, Göran K Hansson, John Andersson
<u>Rationale:</u> Regulatory T (Treg) cells suppress immune responses and have been shown to attenuate atherosclerosis. The Treg cell lineage specification factor FOXP3 is essential for Treg cells' ability to uphold immunological tolerance. In humans, FOXP3 exists in several different isoforms, however, their specific role is poorly understood. <u>Objective:</u> To define the regulation and functions of the two major FOXP3 isoforms, FOXP3fl and FOXP3Δ2, as well as to establish whether their expression is associated with ischemic atherosclerotic disease...
April 4, 2018: Circulation Research
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