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https://www.readbyqxmd.com/read/28646042/on-the-role-il-4-il-13-heteroreceptor-plays-in-regulation-of-type-1-diabetes
#1
Tobechukwu K Ukah, Alexis N Cattin-Roy, Weirong Chen, Mindy M Miller, Subhasis Barik, Habib Zaghouani
Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#2
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28630656/physical-activity-black-carbon-exposure-and-dna-methylation-in-the-foxp3-promoter
#3
Stephanie Lovinsky-Desir, Kyung Hwa Jung, Jacqueline R Jezioro, David Z Torrone, Mariangels de Planell-Saguer, Beizhan Yan, Frederica P Perera, Andrew G Rundle, Matthew S Perzanowski, Steven N Chillrud, Rachel L Miller
BACKGROUND: Physical activity is associated with improvement in lung function; however, pollution exposure during physical activity can lead to a transient reduction in lung function. This paradoxical relationship may be linked to altered T regulatory (Treg) cell activity, which increases with exercise and suppresses airway inflammation, but decreases in association with exposure to air pollution. To clarify these relationships, we investigated buccal cell DNA methylation of the forkhead box p3 (FOXP3) gene promoter, a proposed biomarker of Treg activity...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28630384/modulation-of-cd4-t-cell-subsets-by-euphorbia-microciadia-and-euphorbia-osyridea-plant-extracts
#4
Haideh Namdari, Maryam Izad, Zahra Amirghofran
BACKGROUND: Euphorbia plants are traditionally used in folk medicine for infections, inflammation, and cancer. OBJECTIVES: To investigate the effects of the butanolic extracts of Euphorbia micorociadia and Euphorbia osyridea on specific transcription factors and cytokines expression of T cell subsets. METHODS: Activated mouse splenocytes were cultured in the presence of non-cytotoxic concentrations of the extracts. Cells were evaluated for the gene expressions of T cell transcription factors and cytokines of T helper (Th)1 [T-bet and interferon gamma (IFNγ)], Th17 [retinoic acid receptor related orphan receptor (RORγt) and interleukin (IL)-17], and T regulatory (Treg) cells [forkhead box P3(Foxp3), IL-10, and Transforming growth factor (TGF)-β] using real-time PCR...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28622455/intestinal-metabolites-are-profoundly-altered-in-the-context-of-hla-b27-expression-and-functionally-modulate-disease-in-a-rat-model-of-spondyloarthropathy
#5
Mark Asquith, Sean Davin, Patrick Stauffer, Claire Michell, Cathleen Janowitz, Phoebe Lin, Joe Ensign-Lewis, Jason M Kinchen, Dennis R Koop, Jim Rosenbaum
Objective HLA-B27 associated spondyloarthropathies are associated with an altered intestinal microbiota and bowel inflammation. Therefore, we sought to identify B27-dependent changes in both host and microbial metabolites in the HLA-B27/β2m rat and whether microbiota-derived metabolites could impact disease in this major model of spondyloarthropathy. Methods Cecal contents were collected from 6wk (pre-diseased) and 16wk (diseased) Fischer 344 HLA-B27/β2m transgenic rats and WT controls. Metabolomic profiling was performed by high-throughput gas- and liquid-chromatography-based mass spectrometry...
June 16, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28621313/lkb1-maintains-treg-cell-lineage-identity
#6
Di Wu, Yuechen Luo, Wei Guo, Qing Niu, Ting Xue, Fei Yang, Xiaolei Sun, Song Chen, Yuanyuan Liu, Jingru Liu, Zhina Sun, Chunxiao Zhao, Huifang Huang, Fang Liao, Zhongchao Han, Dongming Zhou, Yongguang Yang, Guogang Xu, Tao Cheng, Xiaoming Feng
Regulatory T (Treg) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve Treg lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains Treg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in Treg cells but not in conventional T cells. Mice with Treg cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most Treg cells...
June 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28620375/comparative-gene-expression-analysis-of-lymphocytes-treated-with-exosomes-derived-from-ovarian-cancer-and-ovarian-cysts
#7
Yujuan Li, Yang Yang, Aiwei Xiong, Xiaoqin Wu, Jingyan Xie, Suping Han, Shuli Zhao
Cancer cells employ many strategies to evade immune defense and to facilitate tumor growth and angiogenesis. As a novel mode of intercellular communication, cancer-derived exosomes contribute to the recruitment and mediation of lymphocytes within the tumor environment. However, the mechanisms and key molecules mediating the effect of exosomes on lymphocytes are unclear. We treated healthy peripheral blood lymphocytes with exosomes from ovarian cancer and ovarian cysts and screened for differentially expressed genes using the RT(2) Profiler Cancer Inflammation and Immunity Crosstalk PCR Array...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611777/molecular-signatures-of-human-regulatory-t-cells-in-colorectal-cancer-and-polyps
#8
Nor Adzimah Johdi, Kamel Ait-Tahar, Ismail Sagap, Rahman Jamal
Regulatory T cells (Tregs), a subset of CD4(+) or CD8(+) T cells, play a pivotal role in regulating immune homeostasis. An increase in Tregs was reported in many tumors to be associated with immune suppression and evasion in cancer patients. Despite the importance of Tregs, the molecular signatures that contributed to their pathophysiological relevance remain poorly understood and controversial. In this study, we explored the gene expression profiles in Tregs derived from patients with colorectal cancer [colorectal carcinoma (CRC), n = 15], colorectal polyps (P, n = 15), and in healthy volunteers (N, n = 15)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611475/murine-lrba-deficiency-causes-ctla-4-deficiency-in-tregs-without-progression-to-immune-dysregulation
#9
Deborah Burnett, Ian Parish, Etienne Masle-Farquhar, Robert Brink, Christopher Goodnow
Inherited mutations in Lipopolysaccharide Responsive Beige-like Anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B cell and antibody deficiency (common variable immunodeficiency, CVID), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells, and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 mice carrying a homozygous truncating mutation in Lrba were produced using CRISPR/Cas9-mediated gene targeting...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28611304/immune-profiling-of-nf1-associated-tumors-reveals-histologic-subtype-distinctions-and-heterogeneity-implications-for-immunotherapy
#10
Kellie B Haworth, Michael A Arnold, Christopher R Pierson, Kwangmin Choi, Nicholas D Yeager, Nancy Ratner, Ryan D Roberts, Jonathan L Finlay, Timothy P Cripe
Successful treatment of neurofibromatosis type 1 (NF1)-associated tumors poses a significant clinical challenge. While the primary underlying genetic defect driving RAS signaling is well described, recent evidence suggests immune dysfunction contributes to tumor pathogenesis and malignant transformation. As immunologic characterizations, prognostic and predictive of immunotherapeutic clinical response in other cancers, are not fully described for benign and malignant NF1-related tumors, we sought to define their immunologic profiles...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28607110/the-bile-acid-receptor-gpbar1-regulates-the-m1-m2-phenotype-of-intestinal-macrophages-and-activation-of-gpbar1-rescues-mice-from-murine-colitis
#11
Michele Biagioli, Adriana Carino, Sabrina Cipriani, Daniela Francisci, Silvia Marchianò, Paolo Scarpelli, Daniele Sorcini, Angela Zampella, Stefano Fiorucci
GPBAR1 (TGR5 or M-BAR) is a G protein-coupled receptor for secondary bile acids that is highly expressed in monocytes/macrophages. In this study, we aimed to determine the role of GPBAR1 in mediating leukocyte trafficking in chemically induced models of colitis and investigate the therapeutic potential of BAR501, a small molecule agonist for GPBAR1. These studies demonstrated that GPBAR1 gene ablation enhanced the recruitment of classically activated macrophages in the colonic lamina propria and worsened the severity of inflammation...
June 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28606589/regulatory-effects-of-interleukin-il-15-on-allergen-induced-airway-obstruction
#12
Sathisha Upparahalli Venkateshaiah, Xiang Zhu, Priya Rajavelu, Rituraj Niranjan, Murli Manohar, Alok K Verma, Joseph A Lasky, Anil Mishra
BACKGROUND: Airway obstruction is a physiologic feature of asthma and IL-15 may have an important role in the pathogenesis of asthma. OBJECTIVE: We tested the hypothesis that regulation of IL-15 is critical for the preservation of allergen-induced airway hyperresponsiveness (AHR), airway resistance and compliance in response to methacholine. METHODS: Airway inflammation, AHR, resistance and compliance were assessed in IL-15- gene deficient mice and IL-15 overexpressing mice in an allergen-induced murine model of asthma...
June 9, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28602842/immune-responses-and-parasitological-observations-induced-during-probiotic-treatment-with-medicinal-trichuris-suis-ova-in-a-healthy-volunteer
#13
Andrew R Williams, Anders Dige, Tue Kruse Rasmussen, Christian L Hvas, Jens F Dahlerup, Lars Iversen, C Rune Stensvold, Jørgen Agnholt, Peter Nejsum
Ingestion of eggs (ova) of the porcine nematode parasite Trichuris suis (TSO) may reduce the severity of autoimmune disorders, however the development of TSO treatment as a useful therapy for autoimmune diseases is hampered by a lack of knowledge on the development of the parasite and the nature of the local immune responses in humans. Here, we used colonoscopy to investigate the development of T. suis and related mucosal and systemic immune responses during TSO treatment in an intestinally healthy male volunteer...
June 8, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28600287/enrichment-of-human-ccr6-regulatory-t-cells-with-superior-suppressive-activity-in-oral-cancer
#14
Jang-Jaer Lee, Kung-Chi Kao, Yen-Ling Chiu, Chiau-Jing Jung, Chung-Ji Liu, Shih-Jung Cheng, Yen-Liang Chang, Jenq-Yuh Ko, Jean-San Chia
Human oral squamous cell carcinoma (OSCC) constitutes an inflammatory microenvironment enriched with chemokines such as CCL20, which promote cancer cell invasion and tumor progression. We found that in OSCC there is a correlation between the expression of CCL20 and FOXP3 mRNA. Therefore, we hypothesized that OSCC may favor the recruitment and retention of regulatory T (Treg) cells that express the CCL20 receptor, CCR6. Interestingly, most (∼60%) peripheral blood Treg cells express CCR6, and CCR6(+) Treg cells exhibit an activated effector/memory phenotype...
June 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28600182/mesenchymal-stem-cells-can-induce-regulatory-t-cells-via-modulating-mir-126a-but-not-mir-10a
#15
Maryam Khosravi, Mohammad Hossein Karimi, Mahdokht Hossein Aghdaie, Mehdi Kalani, Sina Naserian, Ali Bidmeshkipour
Among the different immunosuppressive properties attributed to mesenchymal stem cells (MSCs), one relies on their ability to induce regulatory T cells (iTregs) from conventional T cells under particular inflammatory context. Stable Foxp3 expression plays a major role in the phenotypic and functional stability of iTregs. However, the mechanism behind Foxp3 induction in iTregs by MSCs remains unknown. Here, we assessed the possible effect of MSCs on miR-126a and miR-10a expression in iTregs and, consequently on Foxp3 stability, a regulatory pathway that has not yet been explored...
June 18, 2017: Gene
https://www.readbyqxmd.com/read/28599246/ablation-of-il-17-expression-moderates-experimental-autoimmune-myasthenia-gravis-disease-severity
#16
Gabriela Aguilo-Seara, Yanchen Xie, Jarrod Sheehan, Linda L Kusner, Henry J Kaminski
An array of cytokines influences the pathogenesis of early onset myasthenia gravis (MG) and its animal model, experimental autoimmune myasthenia gravis (EAMG). Patients with MG, in particular those with more severe weakness, have elevations of the pro-inflammatory cytokine IL-17 in the blood. We assessed the role of IL-17A in autoimmunity by inducing EAMG in mice with knockout of IL-17 and found a reduction of EAMG severity, but not a complete ablation of disease. The IL-17(ko) mice had no evidence of weakness, low levels of acetylcholine receptor antibodies, and retention of acetylcholine receptor at the neuromuscular junction...
June 6, 2017: Cytokine
https://www.readbyqxmd.com/read/28598035/genetic-study-of-early-onset-graves-disease-in-the-chinese-han-population
#17
Fei-Fei Yuan, Xiao-Ping Ye, Wei Liu, Li-Qiong Xue, Yu-Ru Ma, Le-Le Zhang, Man-Man Zhang, Feng Sun, Yue-Yue Wan, Qian-Yue Zhang, Shuang-Xia Zhao, Huai-Dong Song
Graves' disease (GD) is a complex autoimmune disorder in which genetic and environmental factors are both involved in the pathogenesis. Early-onset patients have a shorter exposure time to environmental factors and are, therefore, good models to help understand the genetic architecture of GD. Based on previous studies of early-onset GD, eleven single nucleotide polymorphisms (SNPs) and their related SNPs (R(2) > 0.6), SNPs located within a ± 1-Mb region of the FOXP3 gene, and twenty validated GD-risk SNPs were selected and screened for genotyping in 3,735 GD and 4,893 control patients to investigate whether early-onset GD is a subtype of GD with distinct susceptibility genes...
June 9, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28593185/induction-of-colonic-regulatory-t-cells-by-mesalamine-by-activating-the-aryl-hydrocarbon-receptor
#18
Kyoko Oh-Oka, Yuko Kojima, Koichiro Uchida, Kimiko Yoda, Kayoko Ishimaru, Shotaro Nakajima, Jun Hemmi, Hiroshi Kano, Yoshiaki Fujii-Kuriyama, Ryohei Katoh, Hiroyuki Ito, Atsuhito Nakao
BACKGROUND & AIMS: Mesalamine is a first-line drug for treatment of inflammatory bowel diseases (IBD). However, its mechanisms are not fully understood. CD4(+) Foxp3(+) regulatory T cells (Tregs) play a potential role in suppressing IBD. This study determined whether the anti-inflammatory activity of mesalamine is related to Treg induction in the colon. METHODS: We examined the frequencies of Tregs in the colons of wild-type mice, mice deficient for aryl hydrocarbon receptor (AhR(-/-) mice), and bone marrow-chimeric mice lacking AhR in hematopoietic cells (BM-AhR(-/-) mice), following oral treatment with mesalamine...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28592566/combined-immune-checkpoint-blockade-as-a-therapeutic-strategy-for-brca1-mutated-breast-cancer
#19
Emma Nolan, Peter Savas, Antonia N Policheni, Phillip K Darcy, François Vaillant, Christopher P Mintoff, Sathana Dushyanthen, Mariam Mansour, Jia-Min B Pang, Stephen B Fox, Charles M Perou, Jane E Visvader, Daniel H D Gray, Sherene Loi, Geoffrey J Lindeman
Immune checkpoint inhibitors have emerged as a potent new class of anticancer therapy. They have changed the treatment landscape for a range of tumors, particularly those with a high mutational load. To date, however, modest results have been observed in breast cancer, where tumors are rarely hypermutated. Because BRCA1-associated tumors frequently exhibit a triple-negative phenotype with extensive lymphocyte infiltration, we explored their mutational load, immune profile, and response to checkpoint inhibition in a Brca1-deficient tumor model...
June 7, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28588584/protein-arginine-methyltransferase-5-inhibition-upregulates-foxp3-regulatory-t-cells-frequency-and-function-during-the-ulcerative-colitis
#20
Yingxia Zheng, Liya Huang, Wensong Ge, Ming Yang, Yanhui Ma, Guohua Xie, Weiwei Wang, Bingxian Bian, Li Li, Hong Nie, Lisong Shen
Ulcerative colitis (UC) pathogenesis is related to imbalance of immune responses, and the equilibrium between inflammatory T cells and Foxp3(+) regulatory T cells (Tregs) plays an important role in the intestinal homeostasis. Protein arginine methyltransferases (PRMTs) regulate chromatin remodeling and gene expression. Here, we investigated whether inhibition of PRMTs affects colitis pathogenesis in mice and inflammatory bowel disease patients and further explored the underlying mechanisms. In this study, we found that protein arginine N-methyltransferase inhibitor 1 (AMI-1) treatments increased Tregs frequency, function, and reduced colitis incidence...
2017: Frontiers in Immunology
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